Aspirin

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Identification

Summary

Aspirin is a salicylate used to treat pain, fever, inflammation, migraines, and reducing the risk of major adverse cardiovascular events.

Brand Names

Aggrenox, Alka-seltzer, Alka-seltzer Fruit Chews, Anacin, Arthriten Inflammatory Pain, Ascomp, Aspi-cor, Aspir-low, Bayer Aspirin, Bayer Womens, Bc Arthritis, Bc Original Formula, Bufferin, Duoplavin, Durlaza, Ecotrin, Ecpirin, Endodan Reformulated May 2009, Equagesic, Exaprin, Excedrin, Excedrin PM Triple Action, Fasprin, Fiorinal, Goody's Body Pain, Goody's Extra Strength, Goody's PM, Miniprin, Norgesic, Norgesic Forte, Orphengesic, Pamprin Max Formula, Robaxisal, ST. Joseph Aspirin, Stanback Headache Powder Reformulated Jan 2011, Trianal, Trianal C, Vanquish, Vazalore, Yosprala

Generic Name

Acetylsalicylic acid
Commonly known or available as Aspirin

DrugBank Accession Number

DB00945

Background

Also known as Aspirin, acetylsalicylic acid (ASA) is a commonly used drug for the treatment of pain and fever due to various causes. Acetylsalicylic acid has both anti-inflammatory and antipyretic effects. This drug also inhibits platelet aggregation and is used in the prevention of blood clots stroke, and myocardial infarction (MI) ^Label.

Interestingly, the results of various studies have demonstrated that long-term use of acetylsalicylic acid may decrease the risk of various cancers, including colorectal, esophageal, breast, lung, prostate, liver and skin cancer ¹⁵. Aspirin is classified as a non-selective cyclooxygenase (COX) inhibitor ^11,14 and is available in many doses and forms, including chewable tablets, suppositories, extended release formulations, and others ¹⁹.

Acetylsalicylic acid is a very common cause of accidental poisoning in young children. It should be kept out of reach from young children, toddlers, and infants ^Label.

Type

Small Molecule

Groups

Approved, Vet approved

Structure

Similar Structures

Weight: Average: 180.1574
Monoisotopic: 180.042258744
Chemical Formula: C₉H₈O₄

Synonyms

2-Acetoxybenzenecarboxylic acid
2-Acetoxybenzoic acid
Acetylsalicylate
Acetylsalicylsäure
acide 2-(acétyloxy)benzoïque
Acide acétylsalicylique
ácido acetilsalicílico
Acidum acetylsalicylicum
ASA
Aspirin
Aspirina
Azetylsalizylsäure
o-acetoxybenzoic acid
O-acetylsalicylic acid
o-carboxyphenyl acetate
Polopiryna
Salicylic acid acetate

External IDs

BAY1019036
NSC-27223
NSC-406186

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Pharmacology

Indication

Pain, fever, and inflammation

Acetylsalicylic acid (ASA), in the regular tablet form (immediate-release), is indicated to relieve pain, fever, and inflammation associated with many conditions, including the flu, the common cold, neck and back pain, dysmenorrhea, headache, tooth pain, sprains, fractures, myositis, neuralgia, synovitis, arthritis, bursitis, burns, and various injuries. It is also used for symptomatic pain relief after surgical and dental procedures ^Label.

The extra strength formulation of acetylsalicylic acid is also indicated for the management migraine pain with photophobia (sensitivity to light) and phonophobia (sensitivity to sound)^Label.

Other indications

ASA is also indicated for various other purposes, due to its ability to inhibit platelet aggregation. These include:

Reducing the risk of cardiovascular death in suspected cases of myocardial infarction (MI) ^Label.

Reducing the risk of a first non-fatal myocardial infarction in patients, and for reducing the risk of morbidity and mortality in cases of unstable angina and in those who have had a prior myocardial infarction ^Label.

For reducing the risk of transient ischemic attacks (TIA) and to prevent atherothrombotic cerebral infarction (in conjunction with other treatments) ^Label.

For the prevention of thromboembolism after hip replacement surgery ^Label.

For decreasing platelet to platelet adhesion following carotid endarterectomy, aiding in the prevention of transient ischemic attacks (TIA) ^Label.

Used for patients undergoing hemodialysis with a silicone rubber arteriovenous cannula inserted to prevent thrombosis at the insertion site ^Label.

Important note regarding use of the extended-release formulation ²²

In the setting of acute myocardial infarction, or before percutaneous interventions, the extended-release form of acetylsalicylic acid should not be used. Use immediate-release formulations in scenarios requiring rapid onset of action ^Label,22. The extended-release form is taken to decrease the incidence of mortality and myocardial infarction (MI) for individuals diagnosed with chronic coronary artery disease (CAD), including patients with previous myocardial infarction (MI) or unstable angina or with chronic stable angina. Additionally, the extended-release form is used to decrease the risk of death and recurrent episodes of stroke in patients with a history of stroke or TIA ²².

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Dose Form
Treatment of	Acute coronary syndrome (acs)		••• •••••
Used in combination to manage	Anxiety	Combination Product in combination with: Meprobamate (DB00371)	••• •••••
Symptomatic treatment of	Arthritis		••••••••••••	••••••• •••••••• •••••••• ••••••• ••••••••• ••••••• ••••••• •••••• ••••••••••••••• ••••••• ••••••• ••••••• •••• ••••••
Prevention of	Atherothrombotic cerebral infarction		••••••••••••
Prevention of	Cardiovascular disease		••• •••••

Associated Therapies

Contraindications & Blackbox Warnings

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Pharmacodynamics

Effects on pain and fever

Acetylsalicylic acid disrupts the production of prostaglandins throughout the body by targeting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) ^9,10,11. Prostaglandins are potent, irritating substances that have been shown to cause headaches and pain upon injection into humans. Prostaglandins increase the sensitivity of pain receptors and substances such as histamine and bradykinin. Through the disruption of the production and prevention of release of prostaglandins in inflammation, this drug may stop their action at pain receptors, preventing symptoms of pain. Acetylsalicylic acid is considered an antipyretic agent because of its ability to interfere with the production of brain prostaglandin E1. Prostaglandin E1 is known to be an extremely powerful fever-inducing agent ^Label.

Effects on platelet aggregation

The inhibition of platelet aggregation by ASA occurs because of its interference with thromboxane A2 in platelets, caused by COX-1 inhibition. Thromboxane A2 is an important lipid responsible for platelet aggregation, which can lead to clot formation and future risk of heart attack or stroke ^Label.

A note on cancer prevention

ASA has been studied in recent years to determine its effect on the prevention of various malignancies ¹⁵. In general, acetylsalicylic acid is involved in the interference of various cancer signaling pathways, sometimes inducing or upregulating tumor suppressor genes ^15,17. Results of various studies suggest that there are beneficial effects of long-term ASA use in the prevention of several types of cancer, including stomach, colorectal, pancreatic, and liver cancers ¹⁶. Research is ongoing.

Mechanism of action

Acetylsalicylic acid (ASA) blocks prostaglandin synthesis. It is non-selective for COX-1 and COX-2 enzymes ^9,10,11. Inhibition of COX-1 results in the inhibition of platelet aggregation for about 7-10 days (average platelet lifespan). The acetyl group of acetylsalicylic acid binds with a serine residue of the cyclooxygenase-1 (COX-1) enzyme, leading to irreversible inhibition. This prevents the production of pain-causing prostaglandins. This process also stops the conversion of arachidonic acid to thromboxane A2 (TXA2), which is a potent inducer of platelet aggregation ^Label. Platelet aggregation can result in clots and harmful venous and arterial thromboembolism, leading to conditions such as pulmonary embolism and stroke.

It is important to note that there is 60% homology between the protein structures of COX-1 and COX-2. ASA binds to serine 516 residue on the active site of COX-2 in the same fashion as its binding to the serine 530 residue located on the active site of COX-1. The active site of COX-2 is, however, slightly larger than the active site of COX-1, so that arachidonic acid (which later becomes prostaglandins) manages to bypass the aspirin molecule inactivating COX-2 ^11,12. ASA, therefore, exerts more action on the COX-1 receptor rather than on the COX-2 receptor ¹⁴. A higher dose of acetylsalicylic acid is required for COX-2 inhibition ¹⁵.

Target	Actions	Organism
AProstaglandin G/H synthase 1	inhibitor	Humans
A3-hydroxy-3-methylglutaryl-coenzyme A reductase	inhibitor	Humans
AProstaglandin G/H synthase 2	inhibitor	Humans
UAldo-keto reductase family 1 member C1	inhibitor	Humans
U5'-AMP-activated protein kinase	activator	Humans
UEndothelin-1 receptor	inhibitor	Humans
UCellular tumor antigen p53	inducer	Humans
UEndoplasmic reticulum chaperone BiP	inhibitor binder	Humans
URibosomal protein S6 kinase alpha-3	inhibitor	Humans
UNF-kappa-B inhibitor alpha	inhibitor	Humans
UTumor necrosis factor-inducible gene 6 protein	inhibitor downregulator	Humans
UCaspase-1	inhibitor downregulator	Humans
UCaspase-3	inhibitor downregulator	Humans
UInhibitor of nuclear factor kappa-B kinase subunit beta	Not Available	Humans
UExtracellular signal-regulated kinase (ERK)	Not Available	Humans
UG1/S-specific cyclin-D1	downregulator	Humans
UMyc proto-oncogene protein	downregulator	Humans
UProliferating cell nuclear antigen	downregulator	Humans
UCyclin A	downregulator
USialidase-1	inhibitor	Humans

Absorption

Absorption is generally rapid and complete following oral administration but absorption may be variable depending on the route, dosage form, and other factors including but not limited to the rate of tablet dissolution, gastric contents, gastric emptying time, and gastric pH ^Label.

Detailed absorption information

When ingested orally, acetylsalicylic acid is rapidly absorbed in both the stomach and proximal small intestine. The non-ionized acetylsalicylic acid passes through the stomach lining by passive diffusion. Ideal absorption of salicylate in the stomach occurs in the pH range of 2.15 - 4.10. Intestinal absorption of acetylsalicylic acid occurs at a much faster rate. At least half of the ingested dose is hydrolyzed to salicylic acid in the first-hour post-ingestion by esterases found in the gastrointestinal tract. Peak plasma salicylate concentrations occur between 1-2 hours post-administration ^Label.

Volume of distribution

This drug is distributed to body tissues shortly after administration. It is known to cross the placenta. The plasma contains high levels of salicylate, as well as tissues such as spinal, peritoneal and synovial fluids, saliva and milk. The kidney, liver, heart, and lungs are also found to be rich in salicylate concentration after dosing. Low concentrations of salicylate are usually low, and minimal concentrations are found in feces, bile, and sweat ^Label.

Protein binding

50% to 90% of a normal therapeutic concentration salicylate (a main metabolite of acetylsalicylic acid ^Label) binds plasma proteins, particularly albumin, while acetylsalicylic acid itself binds negligibly ^Label. Acetylsalicylic acid has the ability to bind to and acetylate many proteins, hormones, DNA, platelets, and hemoglobin ^Label.

Metabolism

Acetylsalicylic acid is hydrolyzed in the plasma to salicylic acid. Plasma concentrations of aspirin following after administration of the extended-release form are mostly undetectable 4-8 hours after ingestion of a single dose. Salicylic acid was measured at 24 hours following a single dose of extended-release acetylsalicylic acid ²².

Salicylate is mainly metabolized in the liver, although other tissues may also be involved in this process ^Label. The major metabolites of acetylsalicylic acid are salicylic acid, salicyluric acid, the ether or phenolic glucuronide and the ester or acyl glucuronide. A small portion is converted to gentisic acid and other hydroxybenzoic acids ^Label.

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Acetylsalicylic acid

Route of elimination

Excretion of salicylates occurs mainly through the kidney, by the processes of glomerular filtration and tubular excretion, in the form of free salicylic acid, salicyluric acid, and, additionally, phenolic and acyl glucuronides ^Label.

Salicylate can be found in the urine soon after administration, however, the entire dose takes about 48 hours to be completely eliminated. The rate of salicylate is often variable, ranging from 10% to 85% in the urine, and heavily depends on urinary pH. Acidic urine generally aids in reabsorption of salicylate by the renal tubules, while alkaline urine increases excretion ^Label.

After the administration of a typical 325mg dose, the elimination of ASA is found to follow first order kinetics in a linear fashion. At high concentrations, the elimination half-life increases ^Label.

Half-life

The half-life of ASA in the circulation ranges from 13 - 19 minutes. Blood concentrations drop rapidly after complete absorption. The half-life of the salicylate ranges between 3.5 and 4.5 hours ^Label.

Clearance

The clearance rate of acetylsalicylic acid is extremely variable, depending on several factors ⁶. Dosage adjustments may be required in patients with renal impairment ^Label. The extended-release tablet should not be administered to patients with eGFR of less than 10 mL/min ²².

Adverse Effects

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Toxicity

Lethal doses

Acute oral LD50 values have been reported as over 1.0 g/kg in humans, cats, and dogs, 0.92 g/kg - 1.48 g/kg in albino rats, 1.19 g/kg in guinea pigs, 1.1 g/kg in mice, and 1.8 g/kg in rabbit models ^Label.

Acute toxicity

Salicylate toxicity is a problem that may develop with both acute and chronic salicylate exposure ⁷. Multiple organ systems may be affected by salicylate toxicity, including the central nervous system, the pulmonary system, and the gastrointestinal system. Severe bleeding may occur. In the majority of cases, patients suffering from salicylate toxicity are volume-depleted at the time of presentation for medical attention. Fluid resuscitation should occur immediately and volume status should be monitored closely. Disruptions in acid-base balance are frequent in ASA toxicity ⁷.

The acute toxicity of acetylsalicylic in animals has been widely studied. The signs of poisoning in rats from lethal doses are mild to severe gastroenteritis, hepatitis, nephritis, pulmonary edema, encephalopathy, shock and some toxic effects on other organs and tissues. Mortality has been observed following convulsions or cardiovascular shock. An important differentiating property between various animal species is the ability to vomit toxic doses. Humans, cats and dogs have this ability, but rodents or rabbits do not ^Label.

Chronic toxicity and carcinogenesis

Chronic ASA toxicity is frequently accompanied by atypical clinical presentations that may be similar to diabetic ketoacidosis, delirium, cerebrovascular accident (CVA), myocardial infarction (MI) or cardiac failure. Plasma salicylate concentrations should be measured if salicylate intoxication is suspected, even if there no documentation available to suggest ASA was ingested. In older age, nephrotoxicity from salicylates increases, and the risk of upper gastrointestinal hemorrhage is increased, with higher rates of mortality ⁸. It is also important to note that ASA toxicity may occur even with close to normal serum concentrations. Prevention of chronic ASA includes the administration of smallest possible doses, avoidance of concurrent use of salicylate drugs, and therapeutic drug monitoring. Renal function should be regularly monitored and screening for gastrointestinal bleeding should be done at regular intervals ⁸.

Chronic toxicity studies were performed in rodents. ASA was administered at doses measured to be 2 to 20 times the maximum tolerated clinical dose to mice for up to one year. Negative dose-related effects were seen. These include decreased mean survival time, decreased number of births and progeny reaching an appropriate age for weaning. No evidence of carcinogenesis was found in 1-year studies ^Label. At daily doses of 0.24 g/kg/day given for 100 days to albino rats, ASA led to signs to excessive thirst, aciduria, diuresis, drowsiness, hyperreflexia, piloerection, changes in respiration, tachycardia, followed by soft stools, epistaxis, sialorrhea, dacryorrhea and mortality during hypothermic coma in the second study month ^Label.

Use in pregnancy and lactation

While teratogenic effects were observed in animals nearly lethal doses, no evidence suggests that this drug is teratogenic in humans ^Label. It is advisable, however, to avoid ASA use the first and second trimester of pregnancy, unless it is clearly required. If acetylsalicylic acid containing drugs are ingested by a patient attempting to conceive, or during the first and second trimester of pregnancy, the lowest possible dose at the shortest possible duration should be taken ^Label. This drug is contraindicated in the 3rd trimester of pregnancy ^Label.

Pathways

Pathway	Category
Acetylsalicylic Acid Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Cytochrome P450 2C9	CYP2C9*3	(C;C) / (A;C)	C Allele	Effect Directly Studied	Patients with this genotype have reduced metabolism of acetylsalicylic acid.	Details
Leukotriene C4 synthase	---	(A;C) / (C;C)	C allele	ADR Directly Studied	The presence of this genotype in LTC4S may indicate an increased risk of chronic urticaria when treated with acetylsalicylic acid.	Details
Integrin beta-3	GPIIIa PlA2	(C;C) / (C;T)	T > C	Effect Directly Studied	Patients with this genotype have increased resistance to the anti-thrombotic effects of aspirin.	Details
Cytochrome P450 2C9	CYP2C9*6	Not Available	818delA	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*15	Not Available	485C>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*25	Not Available	353_362delAGAAATGGAA	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*35	Not Available	374G>T / 430C>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*2	Not Available	430C>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*4	Not Available	1076T>C	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*5	Not Available	1080C>G	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*8	Not Available	449G>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*11	Not Available	1003C>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*12	Not Available	1465C>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*13	Not Available	269T>C	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*14	Not Available	374G>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*16	Not Available	895A>G	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*18	Not Available	1075A>C / 1190A>C … show all	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*26	Not Available	389C>G	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*28	Not Available	641A>T	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*30	Not Available	1429G>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details
Cytochrome P450 2C9	CYP2C9*33	Not Available	395G>A	Effect Inferred	Poor drug metabolizer, lower dose requirements	Details

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abacavir	Acetylsalicylic acid may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abatacept	The metabolism of Acetylsalicylic acid can be increased when combined with Abatacept.
Abciximab	Acetylsalicylic acid may increase the antiplatelet activities of Abciximab.
Abrocitinib	The risk or severity of bleeding and thrombocytopenia can be increased when Acetylsalicylic acid is combined with Abrocitinib.
Acamprosate	The excretion of Acamprosate can be decreased when combined with Acetylsalicylic acid.

Food Interactions

Avoid alcohol. Alcohol increases the risk of gastrointestinal bleeding.
Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Take after a meal. This reduces irritating gastrointestinal effects.
Take with a full glass of water.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Lysine acetylsalicylate	2JJ274J145	62952-06-1	JJBCTCGUOQYZHK-UHFFFAOYSA-N

Product Images

International/Other Brands

Acenterine / Acetophen (Merck) / Adiro / Aspergum / Aspro / Easprin / Empirin / Nu-seals / Rhodine / Rhonal / Solprin / Solprin acid / St. Joseph Aspirin for Adults / Tasprin

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Durlaza	Capsule, extended release	162.5 mg/1	Oral	New Haven Pharmaceuticals, Inc.	2015-09-25	Not applicable

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
365 Everyday Value Aspirin	Tablet, film coated	325 mg/1	Oral	Whole Foods Market, Inc.	2018-08-23	Not applicable
365 Everyday Value Aspirin	Tablet, film coated	325 mg/1	Oral	Whole Foods Market, Inc.	2021-06-08	Not applicable
7 Select Adult Chewable Aspirin	Tablet, chewable	81 mg/1	Oral	7 Eleven	2014-08-05	2017-08-09
7 Select Aspirin	Tablet, film coated	325 mg/1	Oral	7-Eleven	2014-08-05	2021-03-31
81 mg Low Dose Aspirin	Tablet	81 mg/1	Oral	Big Lots Stores, Inc.	2008-02-12	2013-06-25

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
10 Person ANSI	Acetylsalicylic acid (325 mg/1) + Acetaminophen (325 mg/1) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (0.13 g/100g) + Benzalkonium chloride (0.40 mL/100mL) + Benzocaine (6 mL/100mL) + Ethanol (60 mL/100mL) + Ibuprofen (200 mg/1) + Lidocaine (0.5 1/100g) + Neomycin sulfate (5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL)	Kit	Ophthalmic; Oral; Topical	Genuine First Aid	2010-04-24	Not applicable
217	Acetylsalicylic acid (325 mg / tab) + Caffeine citrate (30 mg / tab)	Tablet	Oral	Merck Frosst Canada & Cie, Merck Frosst Canada & Co.	1910-12-31	1998-04-21
217 Strong Tab	Acetylsalicylic acid (500 mg / tab) + Caffeine citrate (30 mg / tab)	Tablet	Oral	Merck Frosst Canada & Cie, Merck Frosst Canada & Co.	1973-12-31	1998-04-21
222 Tablets	Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg) + Codeine phosphate (8 mg)	Tablet	Oral	Mcneil Consumer Healthcare Division Of Johnson & Johnson Inc	1951-12-31	2015-08-17
25 Person ANSI	Acetylsalicylic acid (325 mg/1) + Acetaminophen (325 mg/1) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (0.13 g/100g) + Benzalkonium chloride (0.40 mL/100mL) + Benzocaine (6 mL/100mL) + Ethanol (60 mL/100mL) + Ethanol (62 g/100g) + Ibuprofen (200 mg/1) + Isopropyl alcohol (70 mL/100mL) + Lidocaine (0.5 g/100g) + Neomycin sulfate (5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL)	Kit	Ophthalmic; Oral; Topical	Genuine First Aid	2010-04-25	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
4032 First Aid Kit	Acetylsalicylic acid (325 mg/1) + Ammonia (0.045 g/0.3mL) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (1.3 mg/1mL) + Lidocaine hydrochloride (24.64 mg/1mL) + Neomycin sulfate (3.5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL)	Inhalant; Kit; Liquid; Ointment; Spray; Tablet	Ophthalmic; Oral; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable
4134 First Aid Kit	Acetylsalicylic acid (325 mg/1) + Benzalkonium chloride (0.13 g/100g) + Benzalkonium chloride (1.3 mg/1mL) + Lidocaine hydrochloride (0.5 g/100g) + Water (98.6 mL/100mL)	Cream; Kit; Liquid; Tablet	Ophthalmic; Oral; Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable
4139 First Aid Kit	Acetylsalicylic acid (325 mg/1) + Ammonia (0.045 g/0.3mL) + Benzalkonium chloride (0.13 g/100g) + Benzalkonium chloride (1.3 mg/1mL) + Lidocaine hydrochloride (0.5 g/100g)	Kit	Oral; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable
4142 First Aid Kit	Acetylsalicylic acid (325 mg/1) + Ammonia (0.045 g/0.3mL) + Benzalkonium chloride (1.3 mg/1mL) + Benzethonium chloride (0.2 g/100g) + Benzocaine (10 g/100g) + Lidocaine hydrochloride (2 g/100g) + Water (98.6 mL/100mL)	Kit	Ophthalmic; Oral; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable
4154 First Aid Kit	Acetylsalicylic acid (325 mg/1) + Ammonia (0.045 g/0.3mL) + Benzalkonium chloride (0.13 g/100g) + Benzalkonium chloride (1.3 mg/1mL) + Lidocaine hydrochloride (0.5 g/100g)	Kit	Oral; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable

Chemical Identifiers

UNII: R16CO5Y76E
CAS number: 50-78-2
InChI Key: BSYNRYMUTXBXSQ-UHFFFAOYSA-N
InChI: InChI=1S/C9H8O4/c1-6(10)13-8-5-3-2-4-7(8)9(11)12/h2-5H,1H3,(H,11,12)
IUPAC Name: 2-(acetyloxy)benzoic acid
SMILES: CC(=O)OC1=CC=CC=C1C(O)=O

References

Synthesis Reference

Marino Gobetti, Guido Vandoni, "Acetylsalicylic acid thioesters, a process for their preparation and pharmaceutical compositions containing them." U.S. Patent US4563443, issued March, 1981.

US4563443

General References

Macdonald S: Aspirin use to be banned in under 16 year olds. BMJ. 2002 Nov 2;325(7371):988. [Article]
Sneader W: The discovery of aspirin: a reappraisal. BMJ. 2000 Dec 23-30;321(7276):1591-4. [Article]
Aukerman G, Knutson D, Miser WF: Management of the acute migraine headache. Am Fam Physician. 2002 Dec 1;66(11):2123-30. [Article]
Authors unspecified: Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988 Aug 13;2(8607):349-60. [Article]
Dorsch MP, Lee JS, Lynch DR, Dunn SP, Rodgers JE, Schwartz T, Colby E, Montague D, Smyth SS: Aspirin resistance in patients with stable coronary artery disease with and without a history of myocardial infarction. Ann Pharmacother. 2007 May;41(5):737-41. Epub 2007 Apr 24. [Article]
Levy G: Clinical pharmacokinetics of aspirin. Pediatrics. 1978 Nov;62(5 Pt 2 Suppl):867-72. [Article]
Authors unspecified: Guidance document: management priorities in salicylate toxicity. J Med Toxicol. 2015 Mar;11(1):149-52. doi: 10.1007/s13181-013-0362-3. [Article]
Durnas C, Cusack BJ: Salicylate intoxication in the elderly. Recognition and recommendations on how to prevent it. Drugs Aging. 1992 Jan-Feb;2(1):20-34. [Article]
Flower R: What are all the things that aspirin does? BMJ. 2003 Sep 13;327(7415):572-3. doi: 10.1136/bmj.327.7415.572. [Article]
Hall MN, Campos H, Li H, Sesso HD, Stampfer MJ, Willett WC, Ma J: Blood levels of long-chain polyunsaturated fatty acids, aspirin, and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2007 Feb;16(2):314-21. [Article]
Vane JR, Botting RM: The mechanism of action of aspirin. Thromb Res. 2003 Jun 15;110(5-6):255-8. [Article]
Vane JR, Bakhle YS, Botting RM: Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 1998;38:97-120. doi: 10.1146/annurev.pharmtox.38.1.97. [Article]
Varga Z, Sabzwari SRA, Vargova V: Cardiovascular Risk of Nonsteroidal Anti-Inflammatory Drugs: An Under-Recognized Public Health Issue. Cureus. 2017 Apr 8;9(4):e1144. doi: 10.7759/cureus.1144. [Article]
Ornelas A, Zacharias-Millward N, Menter DG, Davis JS, Lichtenberger L, Hawke D, Hawk E, Vilar E, Bhattacharya P, Millward S: Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention. Cancer Metastasis Rev. 2017 Jun;36(2):289-303. doi: 10.1007/s10555-017-9675-z. [Article]
Alfonso L, Ai G, Spitale RC, Bhat GJ: Molecular targets of aspirin and cancer prevention. Br J Cancer. 2014 Jul 8;111(1):61-7. doi: 10.1038/bjc.2014.271. Epub 2014 May 29. [Article]
Tsoi KKF, Ho JMW, Chan FCH, Sung JJY: Long-term use of low-dose aspirin for cancer prevention: A 10-year population cohort study in Hong Kong. Int J Cancer. 2018 Dec 21. doi: 10.1002/ijc.32083. [Article]
Li D, Wang P, Yu Y, Huang B, Zhang X, Xu C, Zhao X, Yin Z, He Z, Jin M, Liu C: Tumor-preventing activity of aspirin in multiple cancers based on bioinformatic analyses. PeerJ. 2018 Sep 26;6:e5667. doi: 10.7717/peerj.5667. eCollection 2018. [Article]
Hasan Arif; Sandeep Aggarwal (2018). Salicylic Acid (Aspirin): StatPearls. StatPearls Publishing.
Mayo Clinic website: Salicylate [Link]
Health Canada Product Monograph: Aspirin (acetylsalicylic acid) for oral administration [Link]
FDA Approved Drug Products: SYNALGOS®-DC (aspirin, caffeine, and dihydrocodeine bitartrate) capsules, for oral use, CIII (Jan 2024) [Link]
Durlaza FDA label [File]

External Links

Human Metabolome Database: HMDB0001879
KEGG Drug: D00109
KEGG Compound: C01405
PubChem Compound: 2244
PubChem Substance: 46505803
ChemSpider: 2157
BindingDB: 22360
RxNav: 1191
ChEBI: 15365
ChEMBL: CHEMBL25
ZINC: ZINC000000000053
Therapeutic Targets Database: DAP000843
PharmGKB: PA448497
Guide to Pharmacology: GtP Drug Page
PDBe Ligand: AIN
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
PDRhealth: PDRhealth Drug Page
Wikipedia: Aspirin

PDB Entries

1oxr / 1tgm / 2qqt / 3gcl / 3iaz / 4nsb / 6mqf / 8j3w

FDA label

Download (399 KB)

MSDS

Download (24.2 KB)

Clinical Trials

Clinical Trials Clinical Trial & Rare Diseases Add-on Data Package Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package

Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
Unlock 175K+ rows when you subscribe.View sample data
Not Available	Active Not Recruiting	Not Available	Multiple Sclerosis	1	somestatus	stop reason	just information to hide
Not Available	Completed	Not Available	Coronary Artery Disease (CAD) / Prevention of Atherothrombotic Events / Symptomatic Peripheral Artery Disease (Symptomatic PAD)	1	somestatus	stop reason	just information to hide
Not Available	Completed	Basic Science	Type 2 Diabetes Mellitus	1	somestatus	stop reason	just information to hide
Not Available	Completed	Prevention	Heat Stress Disorders	1	somestatus	stop reason	just information to hide
Not Available	Completed	Supportive Care	Extrauterine Pregnancy / Intrauterine Fetal Growth Restriction / Miscarriage Less Than 12 Gestational Weeks / Pre-Eclampsia / Pregnancy	1	somestatus	stop reason	just information to hide

Pharmacoeconomics

Manufacturers

Bayer healthcare llc

Packagers

A-S Medication Solutions LLC
BASF Corp.
Excellium Pharmaceutical Inc.
Harvest Pharmaceuticals Inc.
Kaiser Foundation Hospital
Major Pharmaceuticals
Mckesson Corp.
Par Pharmaceuticals
Prepak Systems Inc.
Rosedale Therapeutics
Time-Cap Labs
United Research Laboratories Inc.

Dosage Forms

Form	Route	Strength
Tablet	Oral
Inhalant; kit; liquid; ointment; spray; tablet	Ophthalmic; Oral; Respiratory (inhalation); Topical
Cream; kit; liquid; tablet	Ophthalmic; Oral; Topical
Cream; kit; liquid; ointment; swab; tablet	Ophthalmic; Oral; Topical
Kit	Ophthalmic; Oral; Respiratory (inhalation); Topical
Inhalant; kit; liquid; spray; tablet	Ophthalmic; Oral; Respiratory (inhalation); Topical
Cream; inhalant; kit; swab; tablet	Oral; Respiratory (inhalation); Topical
Kit	Oral; Respiratory (inhalation); Topical
Inhalant; kit; liquid; ointment; spray; swab; tablet	Ophthalmic; Oral; Respiratory (inhalation); Topical
Cream; kit; liquid; ointment; spray; tablet	Ophthalmic; Oral; Topical
Cream; kit; liquid; ointment; swab; tablet	Oral; Topical
Kit; liquid; ointment; swab; tablet	Ophthalmic; Oral; Topical
Kit; liquid; ointment; swab; tablet	Oral; Topical
Kit; liquid; ointment; spray; tablet	Ophthalmic; Oral; Topical
Kit	Irrigation; Oral; Respiratory (inhalation); Topical
Kit	Irrigation; Ophthalmic; Oral; Respiratory (inhalation); Topical
Tablet	Oral	250 MG
Tablet; tablet, film coated	Oral
Tablet	Oral	325 mg / tab
Injection, powder, for solution	Intramuscular; Intravenous	1000 mg
Injection, powder, for solution	Intramuscular; Intravenous	500 mg
Injection, powder, for solution	Intravenous; Parenteral	1 g/5ml
Injection, powder, for solution	Intravenous; Parenteral	500 mg/2.5ml
Powder, for solution	Oral	1000 mg
Powder, for solution	Oral	200 mg
Powder, for solution	Oral	500 mg
Suppository	Rectal	0.6 g
Suppository	Rectal	1.3 g
Suppository	Rectal	1300 mg
Suppository	Rectal	600 mg
Injection, powder, for solution
Powder, for solution	Oral
Tablet	Oral	300.000 mg
Granule, effervescent	Oral	9.88 g
Kit; tablet, delayed release; tablet, extended release	Oral
Tablet, delayed release	Oral	81 mg/1
Tablet	Oral	325 1/1
Kit	Oral; Topical
Kit	Topical
Capsule	Oral	25.000 MG
Capsule, extended release	Oral
Tablet, effervescent	Oral	324 mg
Granule, effervescent	Oral
Tablet, effervescent	Oral	325 mg/1
Tablet, effervescent	Oral
Tablet	Oral	324 mg
Capsule	Oral	125 MG
Capsule	Oral	500 MG
Capsule, coated pellets		160 mg
Tablet	Oral	300.00 mg
Tablet, delayed release	Oral	975 mg / tab
Tablet, delayed release	Oral	600 mg / tab
Tablet, delayed release	Oral	650 mg / tab
Suppository	Rectal	150 mg
Suppository	Rectal	650 mg
Capsule, extended release	Oral
Tablet, chewable	Oral	80 mg
Tablet, delayed release	Oral	162 mg
Capsule, delayed release	Oral
Tablet, film coated	Oral	500 mg/1
Tablet	Oral	300 mg
Tablet, delayed release	Oral	81 mg
Gum, chewing	Oral	325 mg / gum
Tablet, film coated	Oral
Suppository	Rectal	300 mg/1
Suppository	Rectal	600 mg/1
Tablet	Oral	325 mg/1
Tablet	Oral	325 g/1
Tablet, coated	Oral	325 mg/1
Tablet, coated	Oral	325 ng/1
Tablet, extended release	Oral	81 mg/1
Tablet, film coated	Oral	325 mg/1
Tablet	Oral	80 mg / tab
Tablet, coated	Oral	100 mg
Tablet	Oral
Tablet, coated	Oral	500 MG
Tablet, delayed release; tablet, extended release	Oral	325 mg / tab
Tablet, delayed release; tablet, extended release	Oral	500 mg / tab
Tablet, delayed release	Oral	81 mg/811
Tablet, chewable	Oral	500 mg
Granule	Oral	500 mg
Tablet, coated	Oral	81 mg/1
Tablet, delayed release	Oral	325 mg / ect
Granule	Oral	500 mg / pck
Tablet, coated	Oral	500 mg/5001
Tablet	Oral	500 mg / tab
Granule	Oral	500 mg / sachet
Tablet	Oral	81 mg/1
Tablet, film coated	Oral	81 mg/1
Tablet, chewable	Oral	81 mg/1
Tablet, film coated	Oral	100 mg
Tablet, delayed release	Oral	100 MG
Powder	Oral	325 mg/1
Granule	Oral
Suppository	Rectal	1 G
Suppository	Rectal	300 mg
Tablet	Oral	100 MG
Tablet	Oral	500.000 mg
Tablet, effervescent	Oral	400 MG
Tablet, effervescent	Oral	400 MG
Pill
Granule, effervescent	Oral	500 mg
Granule	Oral	500.00 mg
Granule, for suspension	Oral	30 MG
Tablet, effervescent	Oral	500 mg
Tablet, coated	Oral
Powder	Oral
Capsule	Oral
Tablet, effervescent	Oral
Tablet	Oral	320 mg
Tablet, delayed release	Oral	75 MG
Tablet, film coated	Oral	30 mg
Tablet	Oral	75 MG
Granule, for suspension	Oral
Tablet, delayed release	Oral	325 mg / tab
Capsule
Aerosol, metered; injection; kit; tablet; tablet, chewable	Intramuscular; Intravenous; Oral; Respiratory (inhalation); Subcutaneous; Sublingual
Tablet	Oral	500 mg/1
Powder	Oral	500 mg/1
Tablet, coated	Oral	500 mg/1
Spray	Oral	6 mg/0.1mL
Lozenge	Oral
Capsule	Oral	100.00 mg
Capsule	Oral
Tablet, orally disintegrating	Oral
Capsule, coated	Oral	100 mg
Tablet	Oral	0.5 G
Tablet	Oral	324 MG
Tablet, delayed release	Oral	10000000 mg
Powder, for solution	Oral	100 MG
Powder, for solution	Oral	160 MG
Powder, for solution	Oral	300 MG
Powder, for solution	Oral	75 MG
Tablet, delayed release	Oral
Capsule	Oral	100 mg
Suppository	Rectal
Tablet, delayed release	Oral	80 mg / tab
Tablet, chewable	Oral
Tablet, film coated	Oral	100 mg
Granule	Oral	300.000 mg
Tablet	Oral	100.000 mg
Aerosol, metered; injection; kit; solution; tablet; tablet, chewable	Intramuscular; Intravenous; Oral; Respiratory (inhalation); Subcutaneous; Sublingual
Paste	Dental
Capsule, extended release	Oral	162.5 mg/1
Tablet, coated	Oral	150 mg
Tablet, delayed release	Oral	150 mg
Capsule, coated	Oral	324 mg
Capsule, coated	Oral	150 mg
Capsule, coated	Oral	300 mg
Capsule, coated	Oral	500 mg
Tablet, delayed release	Oral	325 mg/3251
Tablet, delayed release	Oral	325 mg
Tablet, delayed release	Oral	650 mg
Tablet, chewable	Oral	81 mg
Tablet, delayed release	Oral	500 mg
Tablet, delayed release	Oral	975 mg
Tablet, chewable	Oral	325 mg
Kit; tablet, film coated	Oral
Capsule, gelatin coated	Oral
Tablet, orally disintegrating	Oral	81 mg/1
Tablet	Oral	50 MG
Kit	Ophthalmic; Oral; Topical
Capsule, coated	Oral
Tablet, coated	Oral	162 mg/1621
Tablet, coated	Oral	81 mg/811
Tablet, film coated	Topical
Powder	Oral
Tablet	Oral	300 mg / tab
Tablet, delayed release	Oral	50 mg
Tablet	Oral	500.00 mg
Tablet	Oral	100.00 mg
Capsule	Oral	10.400 mg
Tablet, coated	Oral
Kit	Oral	325 mg/1
Tablet, chewable	Buccal	500 mg
Tablet	Oral	450 mg
Tablet, multilayer	Oral
Tablet, film coated	Oral
Kit; tablet; tablet, delayed release	Oral
Tablet	Oral	81 mg
Tablet, delayed release	Oral	80 mg
Tablet	Oral	100.0 mg
Kit	Oral
Tablet
Tablet	Oral	300.000 mg
Tablet, delayed release	Oral	325 mg/1
Tablet	Oral	80 mg
Strip	Oral	81 mg/1
Powder	Oral	600 mg
Tablet, film coated	Oral	50 mg
Tablet, film coated	Oral	75 mg
Tablet, delayed release	Oral
Tablet, soluble	Oral	300 mg
Tablet	Oral	81 mg/81mg
Tablet	Oral	325 mg/325mg
Capsule	Oral	325 mg/325mg
Capsule	Oral	81 mg/81mg
Tablet	Oral	150 mg
Tablet, effervescent	Oral	350 mg
Tablet, delayed release	Oral	60 mg
Powder	Oral	650 mg/1sachet
Powder, for solution	Oral	162 mg/1sachet
Powder	Oral	162 mg/1sachet
Tablet	Oral	325 mg
Tablet	Oral	162 mg
Tablet	Oral	500 mg
Tablet, film coated	Oral	300 mg
Tablet, film coated	Oral	500 mg
Tablet, delayed release	Oral	300 mg

Prices

Unit description	Cost	Unit
Entrophen 10 650 mg Enteric-Coated Tablet	0.09USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5972916	No	1999-10-26	2017-07-14
US6015577	No	2000-01-18	2017-01-18
US6926907	No	2005-08-09	2023-02-28
US9101637	No	2015-08-11	2022-03-23
US9226892	No	2016-01-05	2032-09-29
US8865187	No	2014-10-21	2022-03-23
US9216150	No	2015-12-22	2032-09-29
US9351984	No	2016-05-31	2021-12-19
US9539214	No	2017-01-10	2033-03-13
US9364439	No	2016-06-14	2022-05-31
US8206741	No	2012-06-26	2023-02-28
US9987231	No	2018-06-05	2033-01-02
US10786444	No	2020-09-29	2032-09-29
US10646431	No	2020-05-12	2032-09-29

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	138-140	http://www.rsc.org/learn-chemistry/content/filerepository/CMP/00/000/045/Aspirin.pdf
boiling point (°C)	140 °C	http://www.chemicalland21.com/lifescience/phar/ACETYLSALICYLIC%20ACID.htm
water solubility	10 mg/mL	https://www.sigmaaldrich.com/catalog/product/sigma/a5376?lang=en®ion=US
logP	1.18	https://www.fip.org/files/fip/BPS/BCS/Monographs/AcetylsalicylicAcid.pdf
pKa	3.5	https://www.fip.org/files/fip/BPS/BCS/Monographs/AcetylsalicylicAcid.pdf

Predicted Properties

Property	Value	Source
logP	1.24	Chemaxon
pKa (Strongest Acidic)	3.41	Chemaxon
pKa (Strongest Basic)	-7.1	Chemaxon
Physiological Charge	-1	Chemaxon
Hydrogen Acceptor Count	3	Chemaxon
Hydrogen Donor Count	1	Chemaxon
Polar Surface Area	63.6 Å²	Chemaxon
Rotatable Bond Count	3	Chemaxon
Refractivity	44.45 m³·mol^-1	Chemaxon
Polarizability	17.1 Å³	Chemaxon
Number of Rings	1	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9645
Blood Brain Barrier	+	0.9376
Caco-2 permeable	-	0.6607
P-glycoprotein substrate	Non-substrate	0.685
P-glycoprotein inhibitor I	Non-inhibitor	0.9118
P-glycoprotein inhibitor II	Non-inhibitor	0.9615
Renal organic cation transporter	Non-inhibitor	0.914
CYP450 2C9 substrate	Non-substrate	0.7518
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Non-substrate	0.7225
CYP450 1A2 substrate	Non-inhibitor	0.9046
CYP450 2C9 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Non-inhibitor	0.9576
CYP450 2C19 inhibitor	Non-inhibitor	0.9445
CYP450 3A4 inhibitor	Non-inhibitor	0.9611
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9557
Ames test	Non AMES toxic	0.9326
Carcinogenicity	Non-carcinogens	0.8356
Biodegradation	Ready biodegradable	0.9067
Rat acute toxicity	2.6386 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9433
hERG inhibition (predictor II)	Non-inhibitor	0.9799

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Download (8.27 KB)

Spectra

Spectrum	Spectrum Type	Splash Key
GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)	GC-MS	splash10-014l-2960000000-ffcb8d28ab7e460b0da8
GC-MS Spectrum - GC-MS (1 TMS)	GC-MS	splash10-006w-2910000000-910e8ce2493a05870b33
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-000f-8900000000-760033c820b78b9452ed
GC-MS Spectrum - EI-B	GC-MS	splash10-00dl-9400000000-64327d3bef0063cf4fe1
GC-MS Spectrum - CI-B	GC-MS	splash10-00di-0900000000-113943b65024522c1712
GC-MS Spectrum - EI-B	GC-MS	splash10-014i-1590000000-7890c99ca2b0e2c4ff19
GC-MS Spectrum - GC-EI-TOF	GC-MS	splash10-014l-2960000000-ffcb8d28ab7e460b0da8
GC-MS Spectrum - GC-MS	GC-MS	splash10-006w-2910000000-910e8ce2493a05870b33
GC-MS Spectrum - GC-EI-TOF	GC-MS	splash10-006w-2900000000-253eb678a85f77d4ba61
Mass Spectrum (Electron Ionization)	MS	splash10-00dl-6900000000-74f8a29aa18d0c3afe98
MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	LC-MS/MS	splash10-00kr-6900000000-324f46e8def1652ed4bf
MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	LC-MS/MS	splash10-000i-9000000000-cdf64eaf75083da6f355
MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	LC-MS/MS	splash10-000i-9000000000-ee75806b6fb8a38fd697
MS/MS Spectrum - EI-B (Unknown) , Positive	LC-MS/MS	splash10-00dl-9400000000-64327d3bef0063cf4fe1
MS/MS Spectrum - CI-B (Unknown) , Positive	LC-MS/MS	splash10-00di-0900000000-113943b65024522c1712
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-000i-1900000000-bc50013edb10656e0aa4
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-000i-2900000000-8c55c1f8d7cb7f247a5d
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-000l-9700000000-d475fd0478daf18a419a
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0006-9100000000-3daaf3c8697e17e67869
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0006-9000000000-ee876bcdd1a5c7c229a0
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0006-9000000000-cd4e1f8fe0a2bbc869f9
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0006-9000000000-4dca49851b5b9fd03d1a
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-00kf-9000000000-4611655c6aff89d706eb
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-014l-9000000000-4d636e2d7318b857528d
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-01ot-0900000000-1256ca04e4244fbc4a64
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-01ot-0900000000-2cae7e19320bfa1a03a0
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-01ot-0900000000-42f69c49b256900b7524
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-01ot-0900000000-4860d5cbeeb9c31311ec
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-006t-3900000000-cc185048e2a1bcc52124
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-01ba-9700000000-ec436cb71e803899f611
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-9100000000-75f611f9e761b63033d9
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-02tc-9000000000-15b9abe0f191aedd9620
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0ik9-9000000000-644d508a79eb48c24ec3
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00di-2900000000-2ab828a7536781de1619
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-000f-9500000000-011bc0f7039840e7abc0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0006-9400000000-19a4db7d336956a3f80c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00di-1900000000-a6b55a2f37579bbedabb
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0006-9000000000-9b2b9c5199bdf878e508
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0htc-9300000000-d6619670e0a60acb8ccb
1H NMR Spectrum	1D NMR	Not Applicable
1H NMR Spectrum	1D NMR	Not Applicable
13C NMR Spectrum	1D NMR	Not Applicable
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable
[1H,13C] 2D NMR Spectrum	2D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	141.5303277	predicted	DarkChem Lite v0.1.0
[M-H]-	142.4774277	predicted	DarkChem Lite v0.1.0
[M-H]-	142.6834277	predicted	DarkChem Lite v0.1.0
[M-H]-	142.6346277	predicted	DarkChem Lite v0.1.0
[M-H]-	131.71933	predicted	DeepCCS 1.0 (2019)
[M+H]+	141.1519277	predicted	DarkChem Lite v0.1.0
[M+H]+	144.2585277	predicted	DarkChem Lite v0.1.0
[M+H]+	143.5771277	predicted	DarkChem Lite v0.1.0
[M+H]+	143.6946277	predicted	DarkChem Lite v0.1.0
[M+H]+	135.44505	predicted	DeepCCS 1.0 (2019)
[M+Na]+	142.0109277	predicted	DarkChem Lite v0.1.0
[M+Na]+	142.5911277	predicted	DarkChem Lite v0.1.0
[M+Na]+	142.6670277	predicted	DarkChem Lite v0.1.0
[M+Na]+	142.7571277	predicted	DarkChem Lite v0.1.0
[M+Na]+	144.68927	predicted	DeepCCS 1.0 (2019)

Targets

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Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	100000	N/A	N/A	A27766
IC 50 (nM)	750410	N/A	N/A	A27769
IC 50 (nM)	560100	N/A	N/A	A29232

Details1. Prostaglandin G/H synthase 1

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:7947975). Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells (Probable). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity)
Specific Function: Heme binding
Gene Name: PTGS1
Uniprot ID: P23219
Uniprot Name: Prostaglandin G/H synthase 1
Molecular Weight: 68685.82 Da

References

Flipo RM: [Are the NSAIDs able to compromising the cardio-preventive efficacy of aspirin?]. Presse Med. 2006 Sep;35(9 Spec No 1):1S53-60. [Article]
Schwartz KA: Aspirin resistance: a review of diagnostic methodology, mechanisms, and clinical utility. Adv Clin Chem. 2006;42:81-110. [Article]
Birnbaum Y, Ye Y, Lin Y, Freeberg SY, Huang MH, Perez-Polo JR, Uretsky BF: Aspirin augments 15-epi-lipoxin A4 production by lipopolysaccharide, but blocks the pioglitazone and atorvastatin induction of 15-epi-lipoxin A4 in the rat heart. Prostaglandins Other Lipid Mediat. 2007 Feb;83(1-2):89-98. Epub 2006 Nov 7. [Article]
Guthikonda S, Lev EI, Patel R, DeLao T, Bergeron AL, Dong JF, Kleiman NS: Reticulated platelets and uninhibited COX-1 and COX-2 decrease the antiplatelet effects of aspirin. J Thromb Haemost. 2007 Mar;5(3):490-6. [Article]
Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Durlaza FDA label [File]

Details2. 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis (PubMed:21357570, PubMed:2991281, PubMed:36745799, PubMed:6995544). HMGCR is the main target of statins, a class of cholesterol-lowering drugs (PubMed:11349148, PubMed:18540668, PubMed:36745799)
Specific Function: Coenzyme a binding
Gene Name: HMGCR
Uniprot ID: P04035
Uniprot Name: 3-hydroxy-3-methylglutaryl-coenzyme A reductase
Molecular Weight: 97475.155 Da

References

Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	18000000	N/A	N/A	A27774
IC 50 (nM)	62500	N/A	N/A	A29233
IC 50 (nM)	1050000	N/A	N/A	A29234
IC 50 (nM)	2400	8	37	A28387
IC 50 (nM)	19800	N/A	N/A	A29235
IC 50 (nM)	100000	N/A	N/A	A28389
IC 50 (nM)	710000	N/A	N/A	A27766
IC 50 (nM)	2400	N/A	N/A	A28402 / A29236 / A28406 / A28407 / A27813 / A27814 / A28423
IC 50 (nM)	1000000	N/A	N/A	A27769
IC 50 (nM)	1413300	N/A	N/A	A29232
Ki (nM)	>10000	N/A	N/A	A5629 / A27471
Ki (nM)	7500	N/A	N/A	A27471

Details3. Prostaglandin G/H synthase 2

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
Specific Function: Enzyme binding
Gene Name: PTGS2
Uniprot ID: P35354
Uniprot Name: Prostaglandin G/H synthase 2
Molecular Weight: 68995.625 Da

References

Hall MN, Campos H, Li H, Sesso HD, Stampfer MJ, Willett WC, Ma J: Blood levels of long-chain polyunsaturated fatty acids, aspirin, and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2007 Feb;16(2):314-21. [Article]
Vane JR, Botting RM: The mechanism of action of aspirin. Thromb Res. 2003 Jun 15;110(5-6):255-8. [Article]
Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Details4. Aldo-keto reductase family 1 member C1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Curator comments: This is a potential target. Supporting data in the literature are limited.

General Function: Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids (PubMed:19218247). Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH (PubMed:14672942). Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens (PubMed:10998348). May also reduce conjugated steroids such as 5alpha-dihydrotestosterone sulfate (PubMed:19218247). Displays affinity for bile acids (PubMed:8486699)
Specific Function: 17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity
Gene Name: AKR1C1
Uniprot ID: Q04828
Uniprot Name: Aldo-keto reductase family 1 member C1
Molecular Weight: 36788.02 Da

References

Dhagat U, Carbone V, Chung RP, Matsunaga T, Endo S, Hara A, El-Kabbani O: A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase. Med Chem. 2007 Nov;3(6):546-50. [Article]

Details5. 5'-AMP-activated protein kinase (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Unknown
Actions: Activator

General Function: Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:37821951). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943)
Specific Function: [acetyl-coa carboxylase] kinase activity

Components:

Name	UniProt ID
5'-AMP-activated protein kinase catalytic subunit alpha-1	Q13131
5'-AMP-activated protein kinase catalytic subunit alpha-2	P54646
5'-AMP-activated protein kinase subunit beta-1	Q9Y478
5'-AMP-activated protein kinase subunit beta-2	O43741
5'-AMP-activated protein kinase subunit gamma-1	P54619
5'-AMP-activated protein kinase subunit gamma-2	Q9UGJ0
5'-AMP-activated protein kinase subunit gamma-3	Q9UGI9

References

Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG: Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology. 2012 Jun;142(7):1504-15.e3. doi: 10.1053/j.gastro.2012.02.050. Epub 2012 Mar 6. [Article]
Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, Kemp BE, Sakamoto K, Steinberg GR, Hardie DG: The ancient drug salicylate directly activates AMP-activated protein kinase. Science. 2012 May 18;336(6083):918-22. doi: 10.1126/science.1215327. Epub 2012 Apr 19. [Article]
Steinberg GR, Dandapani M, Hardie DG: AMPK: mediating the metabolic effects of salicylate-based drugs? Trends Endocrinol Metab. 2013 Oct;24(10):481-7. doi: 10.1016/j.tem.2013.06.002. Epub 2013 Jul 19. [Article]

Details6. Endothelin-1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3
Specific Function: Endothelin receptor activity
Gene Name: EDNRA
Uniprot ID: P25101
Uniprot Name: Endothelin-1 receptor
Molecular Weight: 48721.76 Da

References

Talbodec A, Berkane N, Blandin V, Breittmayer JP, Ferrari E, Frelin C, Vigne P: Aspirin and sodium salicylate inhibit endothelin ETA receptors by an allosteric type of mechanism. Mol Pharmacol. 2000 Apr;57(4):797-804. [Article]
Blandin V, Vigne P, Breittmayer JP, Frelin C: Allosteric inhibition of endothelin ETA receptors by 3, 5-dibromosalicylic acid. Mol Pharmacol. 2000 Dec;58(6):1461-9. [Article]
Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, Pollock DM, Webb DJ, Maguire JJ: Endothelin. Pharmacol Rev. 2016 Apr;68(2):357-418. doi: 10.1124/pr.115.011833. [Article]

Details7. Cellular tumor antigen p53

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inducer

General Function: Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17189187, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:9840937). Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:9840937). One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (PubMed:12524540, PubMed:17189187). Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492)
Specific Function: 14-3-3 protein binding
Gene Name: TP53
Uniprot ID: P04637
Uniprot Name: Cellular tumor antigen p53
Molecular Weight: 43652.79 Da

References

Alfonso LF, Srivenugopal KS, Bhat GJ: Does aspirin acetylate multiple cellular proteins? (Review). Mol Med Rep. 2009 Jul-Aug;2(4):533-7. doi: 10.3892/mmr_00000132. [Article]
Ai G, Dachineni R, Kumar DR, Marimuthu S, Alfonso LF, Bhat GJ: Aspirin acetylates wild type and mutant p53 in colon cancer cells: identification of aspirin acetylated sites on recombinant p53. Tumour Biol. 2016 May;37(5):6007-16. doi: 10.1007/s13277-015-4438-3. Epub 2015 Nov 23. [Article]
Su YF, Yang SH, Lee YH, Wu BC, Huang SC, Liu CM, Chen SL, Pan YF, Chou SS, Chou MY, Yang HW: Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of pentose phosphate pathway. Eur J Pharmacol. 2014 Sep 5;738:101-10. doi: 10.1016/j.ejphar.2014.03.009. Epub 2014 Apr 12. [Article]
Ranganathan S, Joseph J, Mehta JL: Aspirin inhibits human coronary artery endothelial cell proliferation by upregulation of p53. Biochem Biophys Res Commun. 2003 Jan 31;301(1):143-6. [Article]
Luciani MG, Campregher C, Gasche C: Aspirin blocks proliferation in colon cells by inducing a G1 arrest and apoptosis through activation of the checkpoint kinase ATM. Carcinogenesis. 2007 Oct;28(10):2207-17. doi: 10.1093/carcin/bgm101. Epub 2007 May 17. [Article]

Details8. Endoplasmic reticulum chaperone BiP

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Binder
Curator comments: Data regarding this target in relation to acetylsalicylic acid are limited in the literature.

General Function: Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:1550958, PubMed:19538957). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (PubMed:26045166)
Specific Function: Atp binding
Gene Name: HSPA5
Uniprot ID: P11021
Uniprot Name: Endoplasmic reticulum chaperone BiP
Molecular Weight: 72332.425 Da

References

Deng WG, Ruan KH, Du M, Saunders MA, Wu KK: Aspirin and salicylate bind to immunoglobulin heavy chain binding protein (BiP) and inhibit its ATPase activity in human fibroblasts. FASEB J. 2001 Nov;15(13):2463-70. [Article]

Details9. Ribosomal protein S6 kinase alpha-3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity)
Specific Function: Atp binding
Gene Name: RPS6KA3
Uniprot ID: P51812
Uniprot Name: Ribosomal protein S6 kinase alpha-3
Molecular Weight: 83735.325 Da

References

Stevenson MA, Zhao MJ, Asea A, Coleman CN, Calderwood SK: Salicylic acid and aspirin inhibit the activity of RSK2 kinase and repress RSK2-dependent transcription of cyclic AMP response element binding protein- and NF-kappa B-responsive genes. J Immunol. 1999 Nov 15;163(10):5608-16. [Article]
Stratford AL, Dunn SE: The promise and challenges of targeting RSK for the treatment of cancer. Expert Opin Ther Targets. 2011 Jan;15(1):1-4. doi: 10.1517/14728222.2011.537656. [Article]
O'Neill EA: A new target for aspirin. Nature. 1998 Nov 5;396(6706):15, 17. doi: 10.1038/23810. [Article]

Details10. NF-kappa-B inhibitor alpha

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Curator comments: Data in the literature are limited regarding this target action.

General Function: Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:36651806, PubMed:7479976). On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription (PubMed:7479976, PubMed:7628694, PubMed:7796813, PubMed:7878466)
Specific Function: Enzyme binding
Gene Name: NFKBIA
Uniprot ID: P25963
Uniprot Name: NF-kappa-B inhibitor alpha
Molecular Weight: 35608.65 Da

References

Stevenson MA, Zhao MJ, Asea A, Coleman CN, Calderwood SK: Salicylic acid and aspirin inhibit the activity of RSK2 kinase and repress RSK2-dependent transcription of cyclic AMP response element binding protein- and NF-kappa B-responsive genes. J Immunol. 1999 Nov 15;163(10):5608-16. [Article]

Details11. Tumor necrosis factor-inducible gene 6 protein

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Downregulator

General Function: Major regulator of extracellular matrix organization during tissue remodeling (PubMed:15917224, PubMed:18042364, PubMed:26823460). Catalyzes the transfer of a heavy chain (HC) from inter-alpha-inhibitor (I-alpha-I) complex to hyaluronan. Cleaves the ester bond between the C-terminus of the HC and GalNAc residue of the chondroitin sulfate chain in I-alpha-I complex followed by transesterification of the HC to hyaluronan. In the process, potentiates the antiprotease function of I-alpha-I complex through release of free bikunin (PubMed:15917224, PubMed:16873769, PubMed:20463016). Acts as a catalyst in the formation of hyaluronan-HC oligomers and hyaluronan-rich matrix surrounding the cumulus cell-oocyte complex, a necessary step for oocyte fertilization (PubMed:26468290). Assembles hyaluronan in pericellular matrices that serve as platforms for receptor clustering and signaling. Enables binding of hyaluronan deposited on the surface of macrophages to LYVE1 on lymphatic endothelium and facilitates macrophage extravasation. Alters hyaluronan binding to functionally latent CD44 on vascular endothelium, switching CD44 into an active state that supports leukocyte rolling (PubMed:15060082, PubMed:26823460). Modulates the interaction of chemokines with extracellular matrix components and proteoglycans on endothelial cell surface, likely preventing chemokine gradient formation (PubMed:27044744). In a negative feedback mechanism, may limit excessive neutrophil recruitment at inflammatory sites by antagonizing the association of CXCL8 with glycosaminoglycans on vascular endothelium (PubMed:24501198). Has a role in osteogenesis and bone remodeling. Inhibits BMP2-dependent differentiation of mesenchymal stem cell to osteoblasts (PubMed:16771708, PubMed:18586671). Protects against bone erosion during inflammation by inhibiting TNFSF11/RANKL-dependent osteoclast activation (PubMed:18586671)
Specific Function: Calcium ion binding
Gene Name: TNFAIP6
Uniprot ID: P98066
Uniprot Name: Tumor necrosis factor-inducible gene 6 protein
Molecular Weight: 31203.09 Da

References

Shackelford RE, Alford PB, Xue Y, Thai SF, Adams DO, Pizzo S: Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages. Mol Pharmacol. 1997 Sep;52(3):421-9. [Article]
Jiang DQ, Liu H, Zhang SB, Zhang XL: Aspirin inhibits tumor necrosis factor-alpha-stimulated fractalkine expression in human umbilical vein endothelial cells. Chin Med J (Engl). 2009 May 20;122(10):1147-53. [Article]
Kim J, Lee KS, Kim JH, Lee DK, Park M, Choi S, Park W, Kim S, Choi YK, Hwang JY, Choe J, Won MH, Jeoung D, Lee H, Ryoo S, Ha KS, Kwon YG, Kim YM: Aspirin prevents TNF-alpha-induced endothelial cell dysfunction by regulating the NF-kappaB-dependent miR-155/eNOS pathway: Role of a miR-155/eNOS axis in preeclampsia. Free Radic Biol Med. 2017 Mar;104:185-198. doi: 10.1016/j.freeradbiomed.2017.01.010. Epub 2017 Jan 11. [Article]
Kutuk O, Basaga H: Aspirin inhibits TNFalpha- and IL-1-induced NF-kappaB activation and sensitizes HeLa cells to apoptosis. Cytokine. 2004 Mar 7;25(5):229-37. doi: 10.1016/j.cyto.2003.11.007. [Article]

Details12. Caspase-1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Downregulator

General Function: Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active mature peptides (PubMed:15326478, PubMed:15498465, PubMed:1574116, PubMed:26375003, PubMed:32051255, PubMed:37993714, PubMed:7876192, PubMed:9334240). Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a pro-inflammatory response through the cleavage of the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines which are involved in a variety of inflammatory processes (PubMed:15326478, PubMed:15498465, PubMed:1574116, PubMed:32051255, PubMed:7876192). Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:15498465, PubMed:1574116, PubMed:7876192). Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:26375003). In contrast to cleavage of interleukin IL1B, recognition and cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32051255, PubMed:32109412, PubMed:32553275). Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair (PubMed:22464733). Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive (PubMed:28314590). In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly (PubMed:20197547)
Specific Function: Card domain binding
Gene Name: CASP1
Uniprot ID: P29466
Uniprot Name: Caspase-1
Molecular Weight: 45158.215 Da

References

Alfonso L, Ai G, Spitale RC, Bhat GJ: Molecular targets of aspirin and cancer prevention. Br J Cancer. 2014 Jul 8;111(1):61-7. doi: 10.1038/bjc.2014.271. Epub 2014 May 29. [Article]
Pathi S, Jutooru I, Chadalapaka G, Nair V, Lee SO, Safe S: Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors. PLoS One. 2012;7(10):e48208. doi: 10.1371/journal.pone.0048208. Epub 2012 Oct 26. [Article]
Zhang H, Lu J, Jiao Y, Chen Q, Li M, Wang Z, Yu Z, Huang X, Yao A, Gao Q, Xie W, Li L, Yao P: Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function. Front Oncol. 2019 Jan 14;8:679. doi: 10.3389/fonc.2018.00679. eCollection 2018. [Article]
Dhanoya T, Burn J: Colon cancer and Salicylates. Evol Med Public Health. 2016 Apr 15;2016(1):146-7. doi: 10.1093/emph/eow009. Print 2016. [Article]

Details13. Caspase-3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Downregulator

General Function: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430). Following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of many proteins (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:7596430). At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond (PubMed:10497198, PubMed:16374543, PubMed:7596430, PubMed:7774019). Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain (By similarity). Cleaves and activates caspase-6, -7 and -9 (CASP6, CASP7 and CASP9, respectively) (PubMed:7596430). Cleaves and inactivates interleukin-18 (IL18) (PubMed:37993714, PubMed:9334240). Involved in the cleavage of huntingtin (PubMed:8696339). Triggers cell adhesion in sympathetic neurons through RET cleavage (PubMed:21357690). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress (PubMed:23152800). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (PubMed:30878284). Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME) (PubMed:35338844, PubMed:35446120). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, PubMed:33725486)
Specific Function: Aspartic-type endopeptidase activity
Gene Name: CASP3
Uniprot ID: P42574
Uniprot Name: Caspase-3
Molecular Weight: 31607.58 Da

References

Alfonso L, Ai G, Spitale RC, Bhat GJ: Molecular targets of aspirin and cancer prevention. Br J Cancer. 2014 Jul 8;111(1):61-7. doi: 10.1038/bjc.2014.271. Epub 2014 May 29. [Article]
Pathi S, Jutooru I, Chadalapaka G, Nair V, Lee SO, Safe S: Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors. PLoS One. 2012;7(10):e48208. doi: 10.1371/journal.pone.0048208. Epub 2012 Oct 26. [Article]

Details14. Inhibitor of nuclear factor kappa-B kinase subunit beta

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:30337470, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed:17213322, PubMed:19716809). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418)
Specific Function: Atp binding
Gene Name: IKBKB
Uniprot ID: O14920
Uniprot Name: Inhibitor of nuclear factor kappa-B kinase subunit beta
Molecular Weight: 86563.245 Da

References

Alfonso L, Ai G, Spitale RC, Bhat GJ: Molecular targets of aspirin and cancer prevention. Br J Cancer. 2014 Jul 8;111(1):61-7. doi: 10.1038/bjc.2014.271. Epub 2014 May 29. [Article]
Yamamoto Y, Yin MJ, Gaynor RB: IkappaB kinase alpha (IKKalpha) regulation of IKKbeta kinase activity. Mol Cell Biol. 2000 May;20(10):3655-66. [Article]
Konig HG, Watters O, Kinsella S, Ameen M, Fenner BJ, Prehn JHM: A constitutively-active IKK-complex at the axon initial segment. Brain Res. 2018 Jan 1;1678:356-366. doi: 10.1016/j.brainres.2017.10.020. Epub 2017 Oct 24. [Article]
Gamble C, McIntosh K, Scott R, Ho KH, Plevin R, Paul A: Inhibitory kappa B Kinases as targets for pharmacological regulation. Br J Pharmacol. 2012 Feb;165(4):802-19. doi: 10.1111/j.1476-5381.2011.01608.x. [Article]
Yamamoto Y, Gaynor RB: Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest. 2001 Jan;107(2):135-42. doi: 10.1172/JCI11914. [Article]
Rohl M, Pasparakis M, Baudler S, Baumgartl J, Gautam D, Huth M, De Lorenzi R, Krone W, Rajewsky K, Bruning JC: Conditional disruption of IkappaB kinase 2 fails to prevent obesity-induced insulin resistance. J Clin Invest. 2004 Feb;113(3):474-81. doi: 10.1172/JCI18712. [Article]

Details15. Extracellular signal-regulated kinase (ERK) (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Unknown

General Function: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity)
Specific Function: Atp binding

Components:

Name	UniProt ID
Mitogen-activated protein kinase 1	P28482
Mitogen-activated protein kinase 15	Q8TD08
Mitogen-activated protein kinase 3	P27361
Mitogen-activated protein kinase 4	P31152
Mitogen-activated protein kinase 6	Q16659
Mitogen-activated protein kinase 7	Q13164

References

Alfonso L, Ai G, Spitale RC, Bhat GJ: Molecular targets of aspirin and cancer prevention. Br J Cancer. 2014 Jul 8;111(1):61-7. doi: 10.1038/bjc.2014.271. Epub 2014 May 29. [Article]
Wang L, Wu J, Zhang W, Zhi Y, Wu Y, Jiang R, Yang R: Effects of aspirin on the ERK and PI3K/Akt signaling pathways in rats with acute pulmonary embolism. Mol Med Rep. 2013 Nov;8(5):1465-71. doi: 10.3892/mmr.2013.1676. Epub 2013 Sep 10. [Article]
Nishio T, Usami M, Awaji M, Shinohara S, Sato K: Dual effects of acetylsalicylic acid on ERK signaling and Mitf transcription lead to inhibition of melanogenesis. Mol Cell Biochem. 2016 Jan;412(1-2):101-10. doi: 10.1007/s11010-015-2613-x. Epub 2015 Dec 23. [Article]
Weissmann G, Montesinos MC, Pillinger M, Cronstein BN: Non-prostaglandin effects of aspirin III and salicylate: inhibition of integrin-dependent human neutrophil aggregation and inflammation in COX 2- and NF kappa B (P105)-knockout mice. Adv Exp Med Biol. 2002;507:571-7. [Article]

Details16. G1/S-specific cyclin-D1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Downregulator

General Function: Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:33854235, PubMed:8114739, PubMed:8302605). Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Hypophosphorylates RB1 in early G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8302605). Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity (PubMed:15241418). Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (PubMed:9106657). Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner (PubMed:16569215, PubMed:18417529)
Specific Function: Cyclin-dependent protein serine/threonine kinase activator activity
Gene Name: CCND1
Uniprot ID: P24385
Uniprot Name: G1/S-specific cyclin-D1
Molecular Weight: 33728.74 Da

References

Law BK, Waltner-Law ME, Entingh AJ, Chytil A, Aakre ME, Norgaard P, Moses HL: Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. J Biol Chem. 2000 Dec 8;275(49):38261-7. doi: 10.1074/jbc.M005545200. [Article]
Cheng R, Liu YJ, Cui JW, Yang M, Liu XL, Li P, Wang Z, Zhu LZ, Lu SY, Zou L, Wu XQ, Li YX, Zhou Y, Fang ZY, Wei W: Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells. Oncotarget. 2017 May 2;8(18):30252-30264. doi: 10.18632/oncotarget.16325. [Article]
Fan W, Li J, Chen J, Zhu L, Wang Y, Sun B, Hua B, Guo C, Yan Z: Aspirin inhibits the proliferation of synovium-derived mesenchymal stem cells by arresting the cell cycle in the G0/G1 phase. Am J Transl Res. 2017 Nov 15;9(11):5056-5062. eCollection 2017. [Article]

Details17. Myc proto-oncogene protein

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Downregulator

General Function: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3' (PubMed:24940000, PubMed:25956029). Activates the transcription of growth-related genes (PubMed:24940000, PubMed:25956029). Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (PubMed:24940000, PubMed:25956029). Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells (By similarity). Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). Positively regulates transcription of HNRNPA1, HNRNPA2 and PTBP1 which in turn regulate splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808)
Specific Function: Core promoter sequence-specific dna binding
Gene Name: MYC
Uniprot ID: P01106
Uniprot Name: Myc proto-oncogene protein
Molecular Weight: 50564.535 Da

References

Law BK, Waltner-Law ME, Entingh AJ, Chytil A, Aakre ME, Norgaard P, Moses HL: Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. J Biol Chem. 2000 Dec 8;275(49):38261-7. doi: 10.1074/jbc.M005545200. [Article]
Cheng R, Liu YJ, Cui JW, Yang M, Liu XL, Li P, Wang Z, Zhu LZ, Lu SY, Zou L, Wu XQ, Li YX, Zhou Y, Fang ZY, Wei W: Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells. Oncotarget. 2017 May 2;8(18):30252-30264. doi: 10.18632/oncotarget.16325. [Article]
Ai G, Dachineni R, Muley P, Tummala H, Bhat GJ: Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential role in chemoprevention. Tumour Biol. 2016 Feb;37(2):1727-38. doi: 10.1007/s13277-015-3959-0. Epub 2015 Aug 28. [Article]

Details18. Proliferating cell nuclear antigen

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Downregulator

General Function: Auxiliary protein of DNA polymerase delta and epsilon, is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand (PubMed:35585232). Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways (PubMed:24939902). Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion (PubMed:24695737)
Specific Function: Chromatin binding
Gene Name: PCNA
Uniprot ID: P12004
Uniprot Name: Proliferating cell nuclear antigen
Molecular Weight: 28768.48 Da

References

Law BK, Waltner-Law ME, Entingh AJ, Chytil A, Aakre ME, Norgaard P, Moses HL: Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. J Biol Chem. 2000 Dec 8;275(49):38261-7. doi: 10.1074/jbc.M005545200. [Article]
Krishnan K, Aoki T, Ruffin MT, Normolle DP, Boland CR, Brenner DE: Effects of low dose aspirin (81 mg) on proliferating cell nuclear antigen and Amaranthus caudatus labeling in normal-risk and high-risk human subjects for colorectal cancer. Cancer Detect Prev. 2004;28(2):107-13. doi: 10.1016/j.cdp.2004.01.001. [Article]
Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG: Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology. 2012 Jun;142(7):1504-15.e3. doi: 10.1053/j.gastro.2012.02.050. Epub 2012 Mar 6. [Article]

19. Cyclin A

Kind

Group

Organism

Not Available

Pharmacological action

Unknown

Actions

Downregulator

References

Law BK, Waltner-Law ME, Entingh AJ, Chytil A, Aakre ME, Norgaard P, Moses HL: Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. J Biol Chem. 2000 Dec 8;275(49):38261-7. doi: 10.1074/jbc.M005545200. [Article]
Dachineni R, Ai G, Kumar DR, Sadhu SS, Tummala H, Bhat GJ: Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic Acid: A Potential Role in Cancer Prevention. Mol Cancer Res. 2016 Mar;14(3):241-52. doi: 10.1158/1541-7786.MCR-15-0360. Epub 2015 Dec 18. [Article]

Details20. Sialidase-1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage
Specific Function: Alpha-sialidase activity
Gene Name: NEU1
Uniprot ID: Q99519
Uniprot Name: Sialidase-1
Molecular Weight: 45466.96 Da

References

Qorri B, Harless W, Szewczuk MR: Novel Molecular Mechanism of Aspirin and Celecoxib Targeting Mammalian Neuraminidase-1 Impedes Epidermal Growth Factor Receptor Signaling Axis and Induces Apoptosis in Pancreatic Cancer Cells. Drug Des Devel Ther. 2020 Oct 8;14:4149-4167. doi: 10.2147/DDDT.S264122. eCollection 2020. [Article]

Enzymes

Details1. Cytochrome P450 2C19

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inducer
Curator comments: Data found in the literature regarding this enzyme action are currently limited to the results of one study.

General Function: A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
Specific Function: (r)-limonene 6-monooxygenase activity
Gene Name: CYP2C19
Uniprot ID: P33261
Uniprot Name: Cytochrome P450 2C19
Molecular Weight: 55944.565 Da

References

Chen XP, Tan ZR, Huang SL, Huang Z, Ou-Yang DS, Zhou HH: Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. Clin Pharmacol Ther. 2003 Mar;73(3):264-71. doi: 10.1067/mcp.2003.14. [Article]

Details2. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function: (r)-limonene 6-monooxygenase activity
Gene Name: CYP2C9
Uniprot ID: P11712
Uniprot Name: Cytochrome P450 2C9
Molecular Weight: 55627.365 Da

References

Palikhe NS, Kim SH, Nam YH, Ye YM, Park HS: Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria. Allergy Asthma Immunol Res. 2011 Oct;3(4):273-6. doi: 10.4168/aair.2011.3.4.273. Epub 2011 Jul 1. [Article]

Details3. UDP-glucuronosyltransferase 1-6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity)
Specific Function: Enzyme binding
Gene Name: UGT1A6
Uniprot ID: P19224
Uniprot Name: UDP-glucuronosyltransferase 1-6
Molecular Weight: 60750.215 Da

References

Palikhe NS, Kim SH, Nam YH, Ye YM, Park HS: Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria. Allergy Asthma Immunol Res. 2011 Oct;3(4):273-6. doi: 10.4168/aair.2011.3.4.273. Epub 2011 Jul 1. [Article]
Chan AT, Tranah GJ, Giovannucci EL, Hunter DJ, Fuchs CS: Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma. J Natl Cancer Inst. 2005 Mar 16;97(6):457-60. doi: 10.1093/jnci/dji066. [Article]
Chen Y, Kuehl GE, Bigler J, Rimorin CF, Schwarz Y, Shen DD, Lampe JW: UGT1A6 polymorphism and salicylic acid glucuronidation following aspirin. Pharmacogenet Genomics. 2007 Aug;17(8):571-9. doi: 10.1097/01.fpc.0000236339.79916.07. [Article]

Details4. Arylamine N-acetyltransferase 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates (PubMed:12222688, PubMed:7915226). Participates in the detoxification of a plethora of hydrazine and arylamine drugs, and is able to bioactivate several known carcinogens
Specific Function: Arylamine n-acetyltransferase activity
Gene Name: NAT2
Uniprot ID: P11245
Uniprot Name: Arylamine N-acetyltransferase 2
Molecular Weight: 33570.245 Da

References

Palikhe NS, Kim SH, Nam YH, Ye YM, Park HS: Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria. Allergy Asthma Immunol Res. 2011 Oct;3(4):273-6. doi: 10.4168/aair.2011.3.4.273. Epub 2011 Jul 1. [Article]
McDonagh EM, Boukouvala S, Aklillu E, Hein DW, Altman RB, Klein TE: PharmGKB summary: very important pharmacogene information for N-acetyltransferase 2. Pharmacogenet Genomics. 2014 Aug;24(8):409-25. doi: 10.1097/FPC.0000000000000062. [Article]

Transporters

Details1. Solute carrier family 22 member 6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
Specific Function: Alpha-ketoglutarate transmembrane transporter activity
Gene Name: SLC22A6
Uniprot ID: Q4U2R8
Uniprot Name: Solute carrier family 22 member 6
Molecular Weight: 61815.78 Da

References

Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. [Article]
Parvez MM, Shin HJ, Jung JA, Shin JG: Evaluation of para-Aminosalicylic Acid as a Substrate of Multiple Solute Carrier Uptake Transporters and Possible Drug Interactions with Nonsteroidal Anti-inflammatory Drugs In Vitro. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: AAC.02392-16. doi: 10.1128/AAC.02392-16. Print 2017 May. [Article]

Details2. ATP-dependent translocase ABCB1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inducer
Modulator

General Function: Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function: Abc-type xenobiotic transporter activity
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: ATP-dependent translocase ABCB1
Molecular Weight: 141477.255 Da

References

Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. [Article]
Li MP, Tang J, Zhang ZL, Chen XP: Induction of both P-glycoprotein and specific cytochrome P450 by aspirin eventually does not alter the antithrombotic effect of clopidogrel. Clin Pharmacol Ther. 2015 Apr;97(4):324. doi: 10.1002/cpt.32. Epub 2014 Dec 15. [Article]
Oh J, Shin D, Lim KS, Lee S, Jung KH, Chu K, Hong KS, Shin KH, Cho JY, Yoon SH, Ji SC, Yu KS, Lee H, Jang IJ: Aspirin decreases systemic exposure to clopidogrel through modulation of P-glycoprotein but does not alter its antithrombotic activity. Clin Pharmacol Ther. 2014 Jun;95(6):608-16. doi: 10.1038/clpt.2014.49. Epub 2014 Feb 24. [Article]
Kugai M, Uchiyama K, Tsuji T, Yoriki H, Fukui A, Qin Y, Higashimura Y, Mizushima K, Yoshida N, Katada K, Kamada K, Handa O, Takagi T, Konishi H, Yagi N, Yoshikawa T, Shirasaka Y, Tamai I, Naito Y, Itoh Y: MDR1 is related to intestinal epithelial injury induced by acetylsalicylic acid. Cell Physiol Biochem. 2013;32(4):942-50. doi: 10.1159/000354497. Epub 2013 Oct 1. [Article]
Flescher E, Rotem R, Kwon P, Azare J, Jaspers I, Cohen D: Aspirin enhances multidrug resistance gene 1 expression in human Molt-4 T lymphoma cells. Anticancer Res. 2000 Nov-Dec;20(6B):4441-4. [Article]

Details3. Organic anion transporter 3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Specific Function: Organic anion transmembrane transporter activity
Gene Name: SLC22A8
Uniprot ID: Q8TCC7
Uniprot Name: Organic anion transporter 3
Molecular Weight: 59855.585 Da

References

Parvez MM, Shin HJ, Jung JA, Shin JG: Evaluation of para-Aminosalicylic Acid as a Substrate of Multiple Solute Carrier Uptake Transporters and Possible Drug Interactions with Nonsteroidal Anti-inflammatory Drugs In Vitro. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: AAC.02392-16. doi: 10.1128/AAC.02392-16. Print 2017 May. [Article]
Wang C, Wang C, Liu Q, Meng Q, Cang J, Sun H, Peng J, Ma X, Huo X, Liu K: Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat. Drug Metab Dispos. 2014 Jun;42(6):996-1007. doi: 10.1124/dmd.113.055194. Epub 2014 Apr 1. [Article]

Drug created at June 13, 2005 13:24 / Updated at September 12, 2024 23:21

Aspirin

Identification

Structure for Acetylsalicylic acid (DB00945)

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Clinical Trial & Rare Diseases Add-on Data Package

Pharmacoeconomics

Properties

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Collision Cross Sections (CCS)

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Enzymes

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Transporters

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