Diclofenac
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Identification
- Summary
Diclofenac is an NSAID used to treat the signs and symptoms of osteoarthritis and rheumatoid arthritis.
- Brand Names
- Aleve Arthritis Pain, Arthrotec, Cambia, Cataflam, Flector, Licart, Lofena, Pennsaid, Previdolrx Analgesic Pak, Salonpas Pain Relieving Patch, Solaraze, Voltaren, Voltaren Emulgel, Zipsor, Zorvolex
- Generic Name
- Diclofenac
- DrugBank Accession Number
- DB00586
- Background
Diclofenac is a phenylacetic acid derivative and non-steroidal anti-inflammatory drug (NSAID).Label NSAIDs inhibit cyclooxygenase (COX)-1 and-2 which are the enzyme responsible for producing prostaglandins (PGs). PGs contribute to inflammation and pain signalling. Diclofenac, like other NSAIDs, is often used as first line therapy for acute and chronic pain and inflammation from a variety of causes. Diclofenac was the product of rational drug design based on the structures of phenylbutazone, mefenamic acid, and indomethacin.12 The addition of two chlorine groups in the ortho position of the phenyl ring locks the ring in maximal torsion which appears to be related to increased potency. It is often used in combination with misoprostol to prevent NSAID-induced gastric ulcers. Diclofenac was first approved by the FDA in July 1988 under the trade name Voltaren, marketed by Novartis (previously Ciba-Geigy).18
- Type
- Small Molecule
- Groups
- Approved, Vet approved
- Structure
- Weight
- Average: 296.149
Monoisotopic: 295.016684015 - Chemical Formula
- C14H11Cl2NO2
- Synonyms
- [2-(2,6-dichloroanilino)phenyl]acetic acid
- 2-((2,6-dichlorophenyl)amino)benzeneacetic acid
- Diclofenac
- Diclofenac acid
- Diclofenaco
- Diclofenacum
- External IDs
- ISV-205
Pharmacology
- Indication
Diclofenac is indicated for use in the treatment of pain and inflammation from varying sources including inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, as well as injury-related inflammation due to surgery and physical trauma. It is often used in combination with misoprostol as a gastro-protective agent in patients with high risk of developing NSAID-induced ulcers.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Actinic keratosis •••••••••••• Used in combination to treat Acute arthritis Combination Product in combination with: Rabeprazole (DB01129) •••••••••••• ••••••• Used in combination to treat Acute gouty arthritis Combination Product in combination with: Rabeprazole (DB01129) •••••••••••• ••••••• Treatment of Acute migraine •••••••••••• ••••• ••••••• ••• •••••••• Treatment of Acute migraine •••••••••••• •••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever.Label,17 It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach.
- Mechanism of action
Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for production of prostaglandin (PG) G2 which is the precursor to other PGs.Label,17 These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac.
PGE2 is the primary PG involved in modulation of nociception.10 It mediates peripheral sensitization through a variety of effects.17,10 PGE2 activates the Gq-coupled EP1 receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE2 also activates the EP4 receptor, coupled to Gs, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE2 act via EP3 to increase sensitivity to bradykinin and via EP2 to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP2 receptor which couples to Gs. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI2 is known to play a role via its Gs-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.
PGI2 and PGE2 contribute to acute inflammation via their IP and EP2 receptors.17,11 Similarly to β adrenergic receptors these are Gs-coupled and mediate vasodilation through the AC/PKA pathway. PGE2 also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury.17 PGD2 plays a role in the activation of endothelial cell release of cytokines through its DP1 receptor.11 PGI2 and PGE2 modulate T-helper cell activation and differentiation through IP, EP2, and EP4 receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.
PGE2 can cross the blood-brain barrier and act on excitatory Gq EP3 receptors on thermoregulatory neurons in the hypothalamus.17 This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE2 thereby reducing the activity of these neurons.
Target Actions Organism AProstaglandin G/H synthase 2 inhibitorHumans AProstaglandin G/H synthase 1 inhibitorHumans - Absorption
Diclofenac is completely absorbed from the GI tract but likely undergoes significant first pass metabolism with only 60% of the drug reaching systemic circulation unchanged Label,7,8. Many topical formulations are absorbed percutaneous and produce clinically significant plasma concentrations. Absorption is dose proportional over the range of 25-150 mg.7 Tmax varies between formulations with the oral solution reaching peak plasma concentrations in 10-40min, the enteric coated tablet in 1.5-2h, and the sustained- and extended-release formulations prolonging Tmax even further. Administration with food has no significant effects on AUC but does delay Tmax to 2.5-12h.7,8
- Volume of distribution
Diclofenac has a total volume of distribution of 5-10 L or 0.1-0.2 L/kg.7 The volume of the central compartment is 0.04 L/kg.8 Diclofenac distributes to the synovial fluid reaching peak concentration 2-4h after administration.7 There is limited crossing of the blood brain barrier and cerebrospinal fluid concentrations only reach 8.22% of plasma concentrations. Doses of 50 mg delivered via intramuscular injection produced no detectable diclofenac concentrations in breast milk, however metabolite concentrations were not investigated. Diclofenac has been shown to cross the placenta in mice and rats but human data is unavailable.8
- Protein binding
Diclofenac is over 99.7% bound to serum proteins, primarily albumin.7 It is undergoes limited binding to lipoproteins as well with 1.1% bound to HDL, 0.3% to LDL, and 0.15% to VLDL.
- Metabolism
Diclofenac undergoes oxidative metabolism to hydroxy metabolites as well as conjugation to glucuronic acid, sulfate, and taurine.Label,7 The primary metabolite is 4'-hydroxy diclofenac which is generated by CYP2C9. This metabolite is very weakly active with one thirtieth the activity of diclofenac. Other metabolites include 3'-hydroxy diclofenac, 3'-hydroxy-4'methoxy diclofenac, 4',5-dihydroxy diclofenac, an acylglucuronide conjugate, and other conjugate metabolites.
Hover over products below to view reaction partners
- Route of elimination
Diclofenac is mainly eliminated via metabolism.7,8 Of the total dose, 60-70% is eliminated in the urine and 30% is eliminated in the feces. No significant enterohepatic recycling occurs.
- Half-life
The terminal half-life of diclofenac is approximately 2 h, however the apparent half-life including all metabolites is 25.8-33 h.Label,8
- Clearance
Diclofenac has a plasma clearance 16 L/h.8
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain, and gastrointestinal bleeding.Label Hypertension, acute renal failure, respiratory depression and coma occur rarely. In case of overdose, provide supportive care and consider inducing emesis and administering activated charcoal if overdose occurred less than 4 hours prior.
- Pathways
Pathway Category Diclofenac Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
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 Integrate drug-drug
interactions in your softwareAbacavir Diclofenac may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Diclofenac can be increased when it is combined with Abametapir. Abatacept The metabolism of Diclofenac can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Diclofenac is combined with Abciximab. Abiraterone The serum concentration of Diclofenac can be increased when it is combined with Abiraterone. - Food Interactions
- Avoid excessive or chronic alcohol consumption. Co-administration with alcohol may increase the risk of gastrointestinal side effects, such as ulceration.
- Take with food. Food reduces gastric irritation.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Diclofenac deanol 409Q1531N0 81811-14-5 AINBLHPPOHIAEC-UHFFFAOYSA-N Diclofenac diethylamine 6TGQ35Z71K 78213-16-8 ZQVZPANTCLRASL-UHFFFAOYSA-N Diclofenac epolamine X5F8EKL9ZG 119623-66-4 DCERVXIINVUMKU-UHFFFAOYSA-N Diclofenac potassium L4D5UA6CB4 15307-81-0 KXZOIWWTXOCYKR-UHFFFAOYSA-M Diclofenac sodium QTG126297Q 15307-79-6 KPHWPUGNDIVLNH-UHFFFAOYSA-M - Product Images
- International/Other Brands
- Aclonac / Allvoran / Ecofenac / Effekton / Nu-Diclo / Primofenac / Prophenatin / Rhumalgan / Voltarol
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ambator Diclofenac Patch Patch 1 g/10mL Topical 7T Pharma LLC 2017-12-15 2018-03-29 US Cambia Powder, for solution 50 mg/1 Oral Assertio Therapeutics, Inc. 2016-03-10 Not applicable US Cambia Powder, for solution 1 mg/1mg Oral Nautilus Neurosciences, Inc. 2010-04-20 2010-04-23 US Cambia Powder, for solution 1 mg/1mg Oral Nautilus Neurosciences, Inc. 2010-04-20 Not applicable US Cambia Powder, for solution 50 mg / sachet Oral Aralez Pharmaceuticals Canada Inc 2012-06-02 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-diclo Tablet, delayed release 25 mg Oral Apotex Corporation 1989-12-31 Not applicable Canada Apo-diclo Tablet, delayed release 50 mg Oral Apotex Corporation 1989-12-31 Not applicable Canada Apo-diclo Rapide 50 Mg Tablets Tablet 50 mg Oral Apotex Corporation 2001-05-25 Not applicable Canada Apo-diclo SR Tablet, extended release 100 mg / srt Oral Apotex Corporation 1994-12-31 Not applicable Canada Apo-diclo SR Tablet, extended release 75 mg Oral Apotex Corporation 1995-12-31 Not applicable Canada - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aleve Arthritis Pain Gel Gel 1 mg/1g Topical Bayer Healthcare Llc. 2021-06-01 Not applicable US ALMIRAL GEL 1% w/w Gel 1 g/100g Topical MEDOCHEMIE SINGAPORE PTE. LTD. 1991-05-27 Not applicable Singapore Amazon Basic Care Arthritis Pain Gel 10 mg/1g Topical Amazon.com Services LLC 2024-05-15 Not applicable US AMMI VOTARA EMULSTON GEL Gel 1 %w/w Topical บริษัท แมคโครฟาร์ จำกัด 1993-07-15 Not applicable Thailand Arthritis Pain Gel 10 mg/1g Topical Strategic Sourcing Services LLC 2022-07-06 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Act Diclo-miso Diclofenac sodium (75 mg) + Misoprostol (200 mcg) Tablet, delayed release Oral Actavis Pharma Company 2013-03-27 2019-08-08 Canada Act Diclo-miso Diclofenac sodium (50 mg) + Misoprostol (200 mcg) Tablet, delayed release Oral Actavis Pharma Company 2013-03-27 2019-08-08 Canada ADORLAN® FORTE Diclofenac sodium (50 mg) + Tramadol hydrochloride (50 mg) Tablet Oral Grünenthal Colombiana S.A. 2018-08-02 Not applicable Colombia ADORLAN® TABLETAS Diclofenac sodium (25 mg) + Tramadol hydrochloride (25 mg) Tablet Oral Grünenthal Colombiana S.A. 2010-05-12 Not applicable Colombia AFTOJEL % 0,1 + %3 JEL (5 G) Diclofenac sodium (30 mg/g) + Triamcinolone acetonide (1 mg/g) Gel Topical ORVA İLAÇ SAN. VE TİC. A.Ş. 2008-04-30 Not applicable Turkey - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Ambator Diclofenac Patch Diclofenac sodium (1 g/10mL) Patch Topical 7T Pharma LLC 2017-12-15 2018-03-29 US Calcipotriene 0.005% / Diclofenac Sodium 3% / Hyaluronic Acid Sodium Salt 2% / Niacinamide 2% Diclofenac sodium (3 g/100g) + Calcipotriol (0.005 g/100g) + Sodium hyaluronate (2 g/100g) + Nicotinamide (2 g/100g) Cream Topical Sincerus Florida, LLC 2019-05-07 Not applicable US Clofenax Diclofenac sodium (16.05 mg/1mL) Kit; Solution Topical PureTek Corporation 2020-12-09 Not applicable US DermacinRx Lexitral PharmaPak Diclofenac sodium (16.05 mg/1mL) + Capsicum oleoresin (0.25 mg/1mL) Cream; Kit; Solution Topical PureTek Corporation 2015-11-06 2024-04-30 US DermacinRx Lexitral PharmaPak II Diclofenac sodium (16.05 mg/1mL) + Capsicum oleoresin (0.25 mg/1mL) Cream; Kit; Solution Topical PureTek Corporation 2022-03-02 2024-04-30 US
Categories
- ATC Codes
- S01CC01 — Diclofenac and antiinfectives
- S01CC — Antiinflammatory agents, non-steroids and antiinfectives in combination
- S01C — ANTIINFLAMMATORY AGENTS AND ANTIINFECTIVES IN COMBINATION
- S01 — OPHTHALMOLOGICALS
- S — SENSORY ORGANS
- S01BC — Antiinflammatory agents, non-steroids
- S01B — ANTIINFLAMMATORY AGENTS
- S01 — OPHTHALMOLOGICALS
- S — SENSORY ORGANS
- M01AB — Acetic acid derivatives and related substances
- M01A — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
- M01 — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
- M — MUSCULO-SKELETAL SYSTEM
- M02AA — Antiinflammatory preparations, non-steroids for topical use
- M02A — TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
- M02 — TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
- M — MUSCULO-SKELETAL SYSTEM
- M01AB — Acetic acid derivatives and related substances
- M01A — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
- M01 — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
- M — MUSCULO-SKELETAL SYSTEM
- Drug Categories
- Acetic Acid Derivatives and Related Substances
- Acids, Carbocyclic
- Agents causing angioedema
- Agents causing hyperkalemia
- Agents that produce hypertension
- Amines
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)
- Antiinflammatory and Antirheumatic Products
- Antiinflammatory and Antirheumatic Products, Non-Steroids
- Antiinflammatory Preparations, Non-Steroids for Topical Use
- Antimigraine Agents, Miscellaneous
- Antirheumatic Agents
- BSEP/ABCB11 Substrates
- Central Nervous System Agents
- Cyclooxygenase Inhibitors
- Cyclooxygenase-2 (COX-2) Inhibitors
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C18 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Decreased Prostaglandin Production
- Dermatologicals
- Drugs causing inadvertant photosensitivity
- Enzyme Inhibitors
- Ethylamines
- Musculo-Skeletal System
- Nephrotoxic agents
- Non COX-2 selective NSAIDS
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- Ophthalmologicals
- Other Nonsteroidal Anti-inflammatory Agents
- P-glycoprotein inducers
- Peripheral Nervous System Agents
- Phenylacetates
- Photosensitizing Agents
- Sensory Organs
- Sensory System Agents
- Topical Products for Joint and Muscular Pain
- UDP Glucuronosyltransferases Inhibitors
- UGT1A1 Substrates
- UGT1A3 substrates
- UGT1A9 Substrates
- UGT2B17 Inhibitors
- UGT2B7 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Halobenzenes
- Direct Parent
- Dichlorobenzenes
- Alternative Parents
- Aniline and substituted anilines / Aryl chlorides / Amino acids / Secondary amines / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives show 1 more
- Substituents
- 1,3-dichlorobenzene / Amine / Amino acid / Amino acid or derivatives / Aniline or substituted anilines / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Carbonyl group / Carboxylic acid show 12 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- monocarboxylic acid, secondary amino compound, dichlorobenzene, aromatic amine, amino acid (CHEBI:47381)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 144O8QL0L1
- CAS number
- 15307-86-5
- InChI Key
- DCOPUUMXTXDBNB-UHFFFAOYSA-N
- InChI
- InChI=1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)
- IUPAC Name
- 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid
- SMILES
- OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl
References
- Synthesis Reference
Takuzo Kamishita, "Gel preparations for topical application of diclofenac sodium." U.S. Patent US4670254, issued October, 1983.
US4670254- General References
- Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C: Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006 Jun 3;332(7553):1302-8. [Article]
- Solomon DH, Avorn J, Sturmer T, Glynn RJ, Mogun H, Schneeweiss S: Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk. Arthritis Rheum. 2006 May;54(5):1378-89. [Article]
- FitzGerald GA, Patrono C: The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001 Aug 9;345(6):433-42. [Article]
- Graham DJ: COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA. 2006 Oct 4;296(13):1653-6. Epub 2006 Sep 12. [Article]
- Brater DC: Renal effects of cyclooxygyenase-2-selective inhibitors. J Pain Symptom Manage. 2002 Apr;23(4 Suppl):S15-20; discussion S21-3. [Article]
- Gan TJ: Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin. 2010 Jul;26(7):1715-31. doi: 10.1185/03007995.2010.486301. [Article]
- Davies NM, Anderson KE: Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls. Clin Pharmacokinet. 1997 Sep;33(3):184-213. doi: 10.2165/00003088-199733030-00003. [Article]
- Todd PA, Sorkin EM: Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1988 Mar;35(3):244-85. doi: 10.2165/00003495-198835030-00004. [Article]
- Kuehl GE, Lampe JW, Potter JD, Bigler J: Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35. doi: 10.1124/dmd.104.002527. Epub 2005 Apr 20. [Article]
- Chen L, Yang G, Grosser T: Prostanoids and inflammatory pain. Prostaglandins Other Lipid Mediat. 2013 Jul-Aug;104-105:58-66. doi: 10.1016/j.prostaglandins.2012.08.006. Epub 2012 Sep 3. [Article]
- Hirata T, Narumiya S: Prostanoids as regulators of innate and adaptive immunity. Adv Immunol. 2012;116:143-74. doi: 10.1016/B978-0-12-394300-2.00005-3. [Article]
- Sallmann AR: The history of diclofenac. Am. J. Med. 1986 Apr 28;80(4):29-33. [Article]
- Bort R, Mace K, Boobis A, Gomez-Lechon MJ, Pfeifer A, Castell J: Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96. [Article]
- Yan Z, Li J, Huebert N, Caldwell GW, Du Y, Zhong H: Detection of a novel reactive metabolite of diclofenac: evidence for CYP2C9-mediated bioactivation via arene oxides. Drug Metab Dispos. 2005 Jun;33(6):706-13. doi: 10.1124/dmd.104.003095. Epub 2005 Mar 11. [Article]
- Boerma JS, Vermeulen NP, Commandeur JN: One-electron oxidation of diclofenac by human cytochrome P450s as a potential bioactivation mechanism for formation of 2'-(glutathion-S-yl)-deschloro-diclofenac. Chem Biol Interact. 2014 Jan 25;207:32-40. doi: 10.1016/j.cbi.2013.11.001. Epub 2013 Nov 15. [Article]
- Kamimura H, Ito S, Nozawa K, Nakamura S, Chijiwa H, Nagatsuka S, Kuronuma M, Ohnishi Y, Suemizu H, Ninomiya S: Formation of the accumulative human metabolite and human-specific glutathione conjugate of diclofenac in TK-NOG chimeric mice with humanized livers. Drug Metab Dispos. 2015 Mar;43(3):309-16. doi: 10.1124/dmd.114.061689. Epub 2014 Dec 11. [Article]
- Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
- Drugs@FDA: Voltaren Delayed Release [Link]
- Health Canada Product Monograph: Diclofenac oral tablets [Link]
- External Links
- Human Metabolome Database
- HMDB0014724
- KEGG Drug
- D07816
- KEGG Compound
- C01690
- PubChem Compound
- 3033
- PubChem Substance
- 46504644
- ChemSpider
- 2925
- BindingDB
- 13066
- 3355
- ChEBI
- 47381
- ChEMBL
- CHEMBL139
- ZINC
- ZINC000000001281
- Therapeutic Targets Database
- DAP000620
- PharmGKB
- PA449293
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- DIF
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Diclofenac
- PDB Entries
- 1dvx / 1nr6 / 1pxx / 1sv9 / 2b17 / 2wek / 3cfq / 3ib0 / 3n8y / 4oj4 … show 10 more
- FDA label
- Download (610 KB)
- MSDS
- Download (73.6 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 dataNot Available Active Not Recruiting Not Available Ankle Sprains 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Prevention Postoperative Pain, Acute 1 somestatus stop reason just information to hide Not Available Approved for Marketing Not Available Osteoarthritis of the Hands 1 somestatus stop reason just information to hide Not Available Completed Not Available Actinic Keratosis (AK) 1 somestatus stop reason just information to hide Not Available Completed Not Available Acute Pancreatitis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Institut biochemique sa
- Xanodyne pharmaceutics inc
- Nautilus neurosciences inc
- Novartis pharmaceuticals corp
- Apotex inc
- Mutual pharmaceutical co inc
- Mylan pharmaceuticals inc
- Sandoz inc
- Teva pharmaceuticals usa inc
- Watson laboratories inc
- Nycomed us inc
- Novartis consumer health inc
- Akorn inc
- Alcon inc
- Apotex inc richmond hill
- Bausch and lomb inc
- Falcon pharmaceuticals ltd
- Nexus pharmaceuticals inc
- Mallinckrodt inc
- Actavis elizabeth llc
- Alphapharm party ltd
- Carlsbad technology inc
- Nostrum laboratories inc
- Pliva inc
- Roxane laboratories inc
- Teva pharmaceuticals usa
- Unique pharmaceutical laboratories
- Biovail laboratories inc
- Dexcel ltd
- Packagers
- 4uOrtho LLC
- Actavis Group
- Advanced Pharmaceutical Services Inc.
- Advantage Dose LLC
- Aidarex Pharmacuticals LLC
- Akorn Inc.
- Alcon Laboratories
- Almirall Hermal GmbH
- Alpharma Pharmaceuticals LLC
- Altergon Italia SRL
- Amerisource Health Services Corp.
- Apotex Inc.
- Apotheca Inc.
- Apothecary Shop Wholesale
- AQ Pharmaceuticals Inc.
- A-S Medication Solutions LLC
- Bausch & Lomb Inc.
- Bioglan Pharmaceuticals Co.
- Biovail Pharmaceuticals
- Bryant Ranch Prepack
- Cardinal Health
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- Dosage Forms
Form Route Strength Gel 10 MG Gel 11600 MG Injection, solution Intravenous Gel Topical 1 mg/1g Solution Intramuscular 75 MG/3ML Patch Topical 1 g/10mL Injection, solution Intramuscular 25 mg/mL Tablet, extended release Oral 100 mg / srt Tablet, film coated Oral 100.0 mg Tablet, film coated Oral 75 mg Solution Ophthalmic 0.1 % w/v Tablet, sugar coated Oral Tablet Oral 100.00 mg Gel Topical 1 g Capsule, delayed release Oral Tablet, film coated Oral Tablet, coated Oral Gel Topical 5 g Capsule, coated Oral 100 mg Tablet, delayed release Oral 120 mg Tablet, delayed release Oral 75 mg Solution Intramuscular 100 mg Capsule, coated Oral 75 mg Gel Topical 0.01 g/1g Solution Topical 1 g Capsule, coated Rectal 100 mg Patch Transdermal 140 mg Cream; kit; solution / drops Topical Gel; kit; solution / drops Topical Spray Cutaneous 40 MG/ML Gel 11.6 MG Powder, for solution Oral 1 mg/1mg Powder, for solution Oral 50 mg/1 Powder, for solution Oral 50 mg / sachet Solution / drops; suspension / drops Suspension Oral 1.500 g Tablet, sugar coated Oral 50 mg/1 Suspension / drops Oral Tablet, sugar coated Oral 25 mg Tablet, sugar coated Oral 50 mg Syrup 50 mg Tablet Oral 25.000 mg Gel Topical 5 % Powder, for solution Oral 50 mg Injection Intramuscular 75 mg/3ml Spray Solution Ophthalmic 1.000 mg Tablet, effervescent Gel Topical 50 G Injection, solution 25 MG/ML Capsule, extended release Oral Injection, solution Intramuscular; Intravenous 75 mg/3mL Suspension Oral 180.000 mg Kit Oral; Topical Cream; kit; solution Topical Suppository Rectal 100 mg/1 Tablet, extended release Oral 150 mg/1 Suppository Rectal 50 mg/1 Tablet, extended release Oral 75 mg/1 Tablet, for solution; tablet, for suspension Oral 50 mg/1 Tablet, film coated Oral Tablet Oral 75 mg Injection, solution Parenteral 75 MG Capsule, extended release Oral 75 mg/1 Capsule, extended release Oral 100 mg/1 Gel Topical 10 MG Gel Topical Capsule, delayed release Oral 75 mg/1 Capsule Oral Tablet, coated Oral 100 mg Injection, solution Intramuscular; Intravenous 75 mg/2mL Patch Topical Injection, solution Intramuscular; Parenteral 75 MG/3ML Aerosol Topical 1 % Capsule, liquid filled Oral Tablet Oral 100 mg Injection, solution Tablet, soluble Oral Injection, solution Intramuscular 75 MG/3ML Gel 3 % Aerosol, foam Drug delivery system Topical 0.013 g/1 Patch Topical 0.013 g/1 Injection, solution Parenteral 75 MG/3ML Solution Intravenous 0.075 g Solution Parenteral 75 mg Tablet, effervescent Oral 25 MG Tablet, effervescent Oral 50 MG Plaster Cutaneous Tablet Oral Tablet Oral 50 mg/1 Tablet, coated Oral 25 mg/1 Tablet, coated Oral 50 mg/1 Tablet, film coated Oral 50 mg/1 Tablet, for solution; tablet, for suspension Oral 50 MG Capsule, extended release Oral 75 MG Injection, solution Parenteral 75 MG/2ML Gel Topical 1.0 g/100g Tablet, for suspension Oral 50 mg Tablet, extended release Oral 150 MG Injection Tablet, extended release Oral Injection, solution Intramuscular Aerosol, metered Topical 30 mg/1mL Gel Topical 10 mg/1 Gel Topical 3 g/100g Gel Topical 30 mg/1g Solution Topical 16.05 mg/1mL Solution / drops Ophthalmic 1 mg/1mL Solution / drops Ophthalmic 3.5 mg/1mL Solution / drops Transdermal 16.05 mg/1mL Tablet Oral 25 mg/1 Tablet Oral 75 mg/1 Tablet, delayed release Oral 25 mg/1 Tablet, delayed release Oral 50 mg/1 Tablet, delayed release Oral 75 mg/1 Tablet, film coated Oral 100 mg/1 Tablet, film coated, extended release Oral 100 mg/1 Cream Topical 300 mg/1g Tablet, delayed release Oral Tablet, extended release Oral 100 mg/1 Gel Topical 1 mg/100g Gel Topical 1 g/100g Gel Topical 10 MG/G Gel Topical 20 MG/G Solution Intramuscular 75 U Solution Intraocular; Ophthalmic 1 mg Solution Intramuscular 75 mg Solution Intramuscular; Intravenous 75 mg Injection Parenteral 75 mg Tablet Oral 150 mg Tablet, coated Oral 5000000 mg Injection 25 mg Solution / drops Ophthalmic Solution / drops Ophthalmic 1 MG/ML Gel Topical 1 % w/w Capsule, delayed release Oral 75 MG Mouthwash Oral Spray Oral Rinse Oral 200 ml Capsule, extended release Oral 150 MG Granule, for solution Oral 50 MG Solution / drops Oral 25 MG/ML Solution / drops Oral 46.5 MG/ML Tablet Oral 50 MG Aerosol, foam Topical 3 % Patch Topical 180 MG Granule, for solution Oral 25 MG Cream; kit; solution / drops Topical; Transdermal Solution Topical 4.64 % w/v Injection Parenteral 75 mg/mL Injection Intramuscular 75 mg/ml Solution Intramuscular 75.000 mg Cream; gel; kit; solution Topical Gel; kit; solution Topical Gel Topical 1 g/1 Tablet Oral Tablet, coated Oral 50 mg Capsule Oral 100 mg/1 Capsule Oral 200 mg/1 Capsule Oral 50 mg/1 Solution Intramuscular Gel; solution; spray Topical 4 % Injection, solution Intravenous 75 mg/3ml Kit; liquid; solution Topical Solution Ophthalmic 1 mg Solution Oral Granule Oral 65.000 mg Tablet, coated Oral 75 mg Tablet Oral 50 mg Cream Cutaneous 1.000 g Gel Topical 1.000 g Solution Parenteral 75.00 mg Solution Ophthalmic; Topical 1 mg Tablet Oral 0.250 mg Tablet Oral 1.000 mg Tablet Oral 1.00 mg Powder Oral 50 mg Tablet Oral 50.000 mg Solution Intravenous Injection Intramuscular 25 mg/ml Kit Topical 10 mg/1g Tablet, multilayer Oral Injection, solution Intravenous 37.5 mg/1mL Kit; oil; solution / drops Sublingual; Topical Solution Oral 50 MG/ML Tablet Oral 100.000 mg Spray Cutaneous Injection Intramuscular Gel Topical 1000 mg Solution Conjunctival; Ophthalmic 1 mg Suspension Oral 15 mg Tablet, delayed release; tablet, sugar coated Oral 50 MG Patch Topical Patch Topical 0.013 mg/1 Patch Topical 13 mg/1 Patch Topical 180 mg/14g Patch Topical 180 mg/1 Granule Oral 25 MG Plaster Topical 180 mg Patch Topical 1 % Gel Topical 1 % Granule, for solution Oral Injection, solution 50 MG/ML Injection, solution 75 MG/ML Plaster Topical 1 % Cream Topical Solution / drops Oral Suppository Rectal Solution Intramuscular 100.000 mg Tablet Oral 100.000 mg Gel 10 mg/g Injection, solution Subcutaneous Tablet, delayed release Oral Gel; kit; tablet, delayed release Oral; Topical Injection, solution Subcutaneous 25 MG/ML Injection, solution Subcutaneous 50 MG/ML Injection, solution Subcutaneous 75 MG/ML Solution Intramuscular 100.00 mg Kit Topical Patch Topical 140 MG Aerosol, foam Topical Cream Topical 1.000 g Gel Topical 1.160 g Gel; kit; tablet, film coated Oral; Topical Tablet, film coated Oral 25 mg/1 Solution Parenteral 75.000 mg Solution Intramuscular 75.000 mg Capsule, coated pellets Oral Capsule, coated pellets Oral 100 mg Gel Topical 9.3 mg/1g Gel Topical 1.235 g Solution Parenteral Injection Intramuscular 75 mg Cream; kit; tablet, delayed release Oral; Topical Solution / drops Ophthalmic Capsule Oral 100 mg Injection Intramuscular 75 mg/2ml Spray Topical 1 % Gel Topical 10.0 mg/g Patch Topical 60 mg/12g Liquid Topical 16.05 mg/1mL Solution Cutaneous 16 MG/ML Solution Topical 1.5 % w/w Solution Topical 15 mg/1g Solution Topical 16 MG/ML Solution Topical 20 mg/1g Suppository Rectal 12.5 mg Solution Oral 15 mg Solution Intramuscular 7500000 mg Tablet, film coated Oral 100 mg Gel Topical 1 % w/v Tablet Oral 50 mg / tab Gel Topical 50 gr Gel Cutaneous 1.160 g Gel Cutaneous 1.000 g Gel Extracorporeal 3 % Kit Topical 30 mg/1g Gel Cutaneous 30 mg/g Gel Topical 1 g/100mL Tablet Oral 25 mg Capsule Oral Injection, solution Intramuscular 90 mg/3mL Gel Topical Solution Ophthalmic Solution Intramuscular 5.0000 mg Solution Parenteral 75.000 mg Spray Topical 1 % w/w Gel; kit Topical 10 mg/1g Solution Conjunctival; Ophthalmic 0.1 g Solution Intramuscular 125.00 mg Liquid Ophthalmic 0.1 % Suppository Rectal 25 mg Suppository Rectal 50 mg Injection, solution Intramuscular 75 mg Tablet, delayed release Oral 100 mg Gel Cutaneous 1.050 g Gel 1 % w/w Gel Topical 11.6 mg/g Plaster Topical 140 mg Powder, for solution Oral 25 MG Capsule Oral 12.5 MG Capsule Oral 25 MG Suspension Oral 10 MG/5ML Gel Topical 10 mg/1g Gel Topical 2 % Solution Ophthalmic 1 mg/1mL Tablet, soluble Oral 50 mg Suspension Oral 180 mg Patch Topical 30.000 mg Tablet Oral 50.000 mg Injection Intramuscular; Intravenous 75 MG/3ML Gel; kit Topical Tablet, for solution; tablet, for suspension Oral 46.5 MG Capsule Oral 12.500 mg Tablet Oral 12.5 mg Gel Gel 1 % Gel 2 % Gel Topical 1.16 % w/w Gel Topical 100000 g Gel Topical 2.32 % Gel Topical 2.32 % w/w Solution / drops Ophthalmic 0.1 % Solution Ophthalmic 1 mg/ml Tablet, film coated Oral 12.5 mg Capsule Oral 75 mg Gel Topical 23.2 MG/G Gel Topical 1.16 % Tablet Oral 75.000 mg Tablet, extended release Oral 75 mg Gel Topical 2 g Gel Topical 200000 g Tablet, extended release Oral 50 mg Powder 50 mg/1sachet Powder, for solution Oral 50.0 mg Tablet, effervescent Oral Capsule, coated pellets Oral 50 MG Injection 25 mg/ml Solution Intramuscular Ointment Cutaneous Gel Topical 0.0116 g Kit; solution Topical 16.05 mg/1mL Mouthwash Oral 0.074 G/100ML Spray Transmucosal 0.3 MG Capsule, liquid filled Oral 25 mg/1 Capsule Oral 18 mg/1 Capsule Oral 18 MG Capsule Oral 35 MG Capsule Oral 35 mg/1 Tablet, coated Oral Tablet, film coated Oral 25 mg Tablet, film coated Oral 50 mg Gel Topical 1 %w/w Solution 25 mg/1ml Solution Tablet, coated Oral 25 mg Liquid Ophthalmic 1 mg/1ml Tablet, delayed release Oral 25 mg Tablet, delayed release Oral 50 mg Capsule Oral 50 mg Capsule, extended release Oral 100 mg Cream Topical 2 %w/w Tablet, extended release Oral 100 mg Suppository Rectal 100 mg Spray Topical 1 %w/w - Prices
Unit description Cost Unit Voltaren Ophtha 0.1 % Solution 2.73USD ml Voltaren 100 mg Suppository 1.88USD suppository Voltaren Sr 100 mg Sustained-Release Tablet 1.86USD tablet Voltaren 50 mg Suppository 1.4USD suppository Voltaren Sr 75 mg Sustained-Release Tablet 1.31USD tablet Voltaren 50 mg Enteric-Coated Tablet 0.93USD tablet Pms-Diclofenac 100 mg Suppository 0.88USD suppository Sandoz Diclofenac 100 mg Suppository 0.88USD suppository Novo-Difenac Sr 100 mg Sustained-Release Tablet 0.8USD tablet Pms-Diclofenac-Sr 100 mg Sustained-Release Tablet 0.8USD tablet Sandoz Diclofenac Sr 100 mg Sustained-Release Tablet 0.8USD tablet Pms-Diclofenac 50 mg Suppository 0.65USD suppository Sandoz Diclofenac 50 mg Suppository 0.65USD suppository Novo-Difenac Sr 75 mg Sustained-Release Tablet 0.6USD tablet Pms-Diclofenac-Sr 75 mg Sustained-Release Tablet 0.6USD tablet Sandoz Diclofenac Sr 75 mg Sustained-Release Tablet 0.6USD tablet Apo-Diclo 50 mg Enteric-Coated Tablet 0.4USD tablet Novo-Difenac 50 mg Enteric-Coated Tablet 0.4USD tablet Pms-Diclofenac 50 mg Enteric-Coated Tablet 0.4USD tablet Sandoz Diclofenac 50 mg Enteric-Coated Tablet 0.4USD tablet Apo-Diclo 25 mg Enteric-Coated Tablet 0.2USD tablet Novo-Difenac 25 mg Enteric-Coated Tablet 0.2USD tablet Nu-Diclo 25 mg Enteric-Coated Tablet 0.2USD tablet Pms-Diclofenac 25 mg Enteric-Coated Tablet 0.2USD tablet Sandoz Diclofenac 25 mg Enteric-Coated Tablet 0.2USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6407079 No 2002-06-18 2019-06-18 US US8217078 No 2012-07-10 2029-07-10 US US8546450 No 2013-10-01 2030-08-09 US US8618164 No 2013-12-31 2029-07-10 US US8741956 No 2014-06-03 2029-07-10 US US5985850 No 1999-11-16 2015-08-11 US US5792753 No 1998-08-11 2015-08-11 US US5914322 No 1999-06-22 2015-08-11 US US5607690 No 1997-03-04 2019-04-13 US US6974595 No 2005-12-13 2017-05-15 US US7482377 No 2009-01-27 2017-05-15 US US7759394 No 2010-07-20 2026-06-16 US US8097651 No 2012-01-17 2026-06-16 US US8927604 No 2015-01-06 2026-06-16 US US6365180 No 2002-04-02 2019-07-15 US US7662858 No 2010-02-16 2029-02-24 US US7884095 No 2011-02-08 2029-02-24 US US7939518 No 2011-05-10 2029-02-24 US US8110606 No 2012-02-07 2029-02-24 US US8623920 No 2014-01-07 2029-02-24 US US6287594 No 2001-09-11 2019-01-15 US US8946292 No 2015-02-03 2027-03-22 US US9180095 No 2015-11-10 2030-04-23 US US9186328 No 2015-11-17 2030-04-23 US US8999387 No 2015-04-07 2030-04-23 US US9173854 No 2015-11-03 2030-04-23 US US9180096 No 2015-11-10 2030-04-23 US US9017721 No 2015-04-28 2030-04-23 US US8679544 No 2014-03-25 2030-04-23 US US8252838 No 2012-08-28 2028-04-21 US US8563613 No 2013-10-22 2027-10-17 US US8871809 No 2014-10-28 2027-10-17 US US9132110 No 2015-09-15 2027-10-17 US US9220784 No 2015-12-29 2027-10-17 US US9101591 No 2015-08-11 2027-10-17 US US9168305 No 2015-10-27 2027-10-17 US US9066913 No 2015-06-30 2027-10-17 US US9168304 No 2015-10-27 2027-10-17 US US9561200 No 2017-02-07 2029-02-24 US US9370501 No 2016-06-21 2029-07-10 US US9375412 No 2016-06-28 2029-07-10 US US9339552 No 2016-05-17 2027-10-17 US US9539335 No 2017-01-10 2027-10-17 US US9415029 No 2016-08-16 2029-07-10 US US9339551 No 2016-05-17 2027-10-17 US US9827197 No 2017-11-28 2026-06-16 US US11351133 No 2015-02-20 2035-02-20 US US11344520 No 2015-02-20 2035-02-20 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 283-285 °C Not Available water solubility 2.37 mg/L (at 25 °C) FINI,A ET AL. (1986) logP 4.51 AVDEEF,A (1997) pKa 4.15 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.00447 mg/mL ALOGPS logP 4.98 ALOGPS logP 4.26 Chemaxon logS -4.8 ALOGPS pKa (Strongest Acidic) 4 Chemaxon pKa (Strongest Basic) -2.1 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 49.33 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 75.46 m3·mol-1 Chemaxon Polarizability 27.93 Å3 Chemaxon Number of Rings 2 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 + 0.9548 Blood Brain Barrier + 0.9541 Caco-2 permeable + 0.8867 P-glycoprotein substrate Non-substrate 0.7976 P-glycoprotein inhibitor I Non-inhibitor 0.8254 P-glycoprotein inhibitor II Non-inhibitor 0.9548 Renal organic cation transporter Non-inhibitor 0.9086 CYP450 2C9 substrate Non-substrate 0.7779 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.6724 CYP450 1A2 substrate Inhibitor 0.5923 CYP450 2C9 inhibitor Inhibitor 0.6786 CYP450 2D6 inhibitor Non-inhibitor 0.848 CYP450 2C19 inhibitor Non-inhibitor 0.8947 CYP450 3A4 inhibitor Non-inhibitor 0.8647 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6607 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.6706 Biodegradation Not ready biodegradable 0.9719 Rat acute toxicity 3.6447 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9514 hERG inhibition (predictor II) Non-inhibitor 0.868
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 159.517127 predictedDarkChem Lite v0.1.0 [M-H]- 155.47115 predictedDeepCCS 1.0 (2019) [M-H]- 159.517127 predictedDarkChem Lite v0.1.0 [M-H]- 159.517127 predictedDarkChem Lite v0.1.0 [M-H]- 155.47115 predictedDeepCCS 1.0 (2019) [M-H]- 155.47115 predictedDeepCCS 1.0 (2019) [M+H]+ 159.806427 predictedDarkChem Lite v0.1.0 [M+H]+ 157.82915 predictedDeepCCS 1.0 (2019) [M+H]+ 159.806427 predictedDarkChem Lite v0.1.0 [M+H]+ 159.806427 predictedDarkChem Lite v0.1.0 [M+H]+ 157.82915 predictedDeepCCS 1.0 (2019) [M+H]+ 157.82915 predictedDeepCCS 1.0 (2019) [M+Na]+ 160.063627 predictedDarkChem Lite v0.1.0 [M+Na]+ 163.92229 predictedDeepCCS 1.0 (2019) [M+Na]+ 160.063627 predictedDarkChem Lite v0.1.0 [M+Na]+ 160.063627 predictedDarkChem Lite v0.1.0 [M+Na]+ 163.92229 predictedDeepCCS 1.0 (2019) [M+Na]+ 163.92229 predictedDeepCCS 1.0 (2019)
Targets
- 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
- Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. [Article]
- Blomme EA, Chinn KS, Hardy MM, Casler JJ, Kim SH, Opsahl AC, Hall WA, Trajkovic D, Khan KN, Tripp CS: Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice. Br J Dermatol. 2003 Feb;148(2):211-23. [Article]
- Beubler E: [Pharmacology of cyclooxygenase 2 inhibition]. Wien Med Wochenschr. 2003;153(5-6):95-9. [Article]
- Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. [Article]
- Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ: A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003 Nov 14;278(46):45763-9. Epub 2003 Aug 18. [Article]
- 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
- Calkin AC, Sudhir K, Honisett S, Williams MR, Dawood T, Komesaroff PA: Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2. J Clin Endocrinol Metab. 2002 Nov;87(11):5072-5. [Article]
- Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. [Article]
- Kampfer H, Brautigam L, Geisslinger G, Pfeilschifter J, Frank S: Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair. J Invest Dermatol. 2003 May;120(5):880-90. [Article]
- Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. [Article]
- Hinz B, Rau T, Auge D, Werner U, Ramer R, Rietbrock S, Brune K: Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003 Sep;74(3):222-35. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- 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
- Mo SL, Zhou ZW, Yang LP, Wei MQ, Zhou SF: New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126. [Article]
- Obach RS, Reed-Hagen AE: Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos. 2002 Jul;30(7):831-7. [Article]
- Leemann T, Transon C, Dayer P: Cytochrome P450TB (CYP2C): a major monooxygenase catalyzing diclofenac 4'-hydroxylation in human liver. Life Sci. 1993;52(1):29-34. [Article]
- Kumar V, Rock DA, Warren CJ, Tracy TS, Wahlstrom JL: Enzyme source effects on CYP2C9 kinetics and inhibition. Drug Metab Dispos. 2006 Nov;34(11):1903-8. doi: 10.1124/dmd.106.010249. Epub 2006 Aug 23. [Article]
- Roth H: Planning information services in the disability field: some essential steps. Int J Rehabil Res. 1989;12(4):439-48. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Bort R, Mace K, Boobis A, Gomez-Lechon MJ, Pfeifer A, Castell J: Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96. [Article]
- Mancy A, Antignac M, Minoletti C, Dijols S, Mouries V, Duong NT, Battioni P, Dansette PM, Mansuy D: Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70. doi: 10.1021/bi991195u. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Data supporting these enzyme actions is limited to in vitro studies.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). 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:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- Karjalainen MJ, Neuvonen PJ, Backman JT: In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin Pharmacol Toxicol. 2008 Aug;103(2):157-65. doi: 10.1111/j.1742-7843.2008.00252.x. [Article]
- Ma Z, Shi X, Zhang G, Guo F, Shan L, Cai J: Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509. doi: 10.1155/2016/5416509. Epub 2016 Mar 10. [Article]
- 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, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). 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:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Bort R, Mace K, Boobis A, Gomez-Lechon MJ, Pfeifer A, Castell J: Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96. [Article]
- Mancy A, Antignac M, Minoletti C, Dijols S, Mouries V, Duong NT, Battioni P, Dansette PM, Mansuy D: Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70. doi: 10.1021/bi991195u. [Article]
- Melet A, Marques-Soares C, Schoch GA, Macherey AC, Jaouen M, Dansette PM, Sari MA, Johnson EF, Mansuy D: Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92. doi: 10.1021/bi0489309. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10702251, PubMed:15470161, PubMed:15472229, PubMed:17442341, PubMed:18674515, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:23756265, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15470161, PubMed:18674515, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:15472229, PubMed:17442341, PubMed:18719240, PubMed:19022937, PubMed:2159463, PubMed:23288867, PubMed:26220143). Also regulates the levels of retinoic acid, a major metabolite of vitamin A involved in apoptosis, cellular growth and differentiation, and embryonic development (PubMed:10702251). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60720.15 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Kuehl GE, Lampe JW, Potter JD, Bigler J: Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35. doi: 10.1124/dmd.104.002527. Epub 2005 Apr 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). 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). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Ngui JS, Tang W, Stearns RA, Shou M, Miller RR, Zhang Y, Lin JH, Baillie TA: Cytochrome P450 3A4-mediated interaction of diclofenac and quinidine. Drug Metab Dispos. 2000 Sep;28(9):1043-50. [Article]
- Tang W: The metabolism of diclofenac--enzymology and toxicology perspectives. Curr Drug Metab. 2003 Aug;4(4):319-29. [Article]
- Masubuchi Y, Ose A, Horie T: Diclofenac-induced inactivation of CYP3A4 and its stimulation by quinidine. Drug Metab Dispos. 2002 Oct;30(10):1143-8. doi: 10.1124/dmd.30.10.1143. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). 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). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Bort R, Mace K, Boobis A, Gomez-Lechon MJ, Pfeifer A, Castell J: Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in retinoid metabolism. Hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may modulate atRA signaling and clearance. 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 (CPR; NADPH-ferrihemoprotein reductase)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C18
- Uniprot ID
- P33260
- Uniprot Name
- Cytochrome P450 2C18
- Molecular Weight
- 55710.075 Da
References
- Bort R, Mace K, Boobis A, Gomez-Lechon MJ, Pfeifer A, Castell J: Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96. [Article]
- Mancy A, Antignac M, Minoletti C, Dijols S, Mouries V, Duong NT, Battioni P, Dansette PM, Mansuy D: Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70. doi: 10.1021/bi991195u. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). 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:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:15472229, PubMed:18674515, PubMed:18719240, PubMed:23288867, PubMed:23756265, PubMed:24641623). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:23756265). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229, PubMed:18719240, PubMed:23288867). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3, essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonists losartan, candesartan and zolarsartan, which can inhibit the effect of angiotensin II (PubMed:18674515)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1A3
- Molecular Weight
- 60337.835 Da
References
- Kuehl GE, Lampe JW, Potter JD, Bigler J: Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35. doi: 10.1124/dmd.104.002527. Epub 2005 Apr 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15470161, PubMed:15472229, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1A9
- Molecular Weight
- 59940.495 Da
References
- Kuehl GE, Lampe JW, Potter JD, Bigler J: Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35. doi: 10.1124/dmd.104.002527. Epub 2005 Apr 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:18719240, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18719240, PubMed:23288867). Catalyzes the glucuronidation of the endogenous estrogen hormones such as estradiol and estriol (PubMed:18719240, PubMed:23288867)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B4
- Uniprot ID
- P06133
- Uniprot Name
- UDP-glucuronosyltransferase 2B4
- Molecular Weight
- 60512.035 Da
References
- Kuehl GE, Lampe JW, Potter JD, Bigler J: Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35. doi: 10.1124/dmd.104.002527. Epub 2005 Apr 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Potentiator
- General Function
- Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:19022417, PubMed:21233389, PubMed:22516296, PubMed:23246375, PubMed:24282679, PubMed:24893149, PubMed:31664810, PubMed:8615788, PubMed:8631361). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:17114001, PubMed:21206090, PubMed:31664810, PubMed:32404334, PubMed:8615788). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity)
- Specific Function
- arachidonate 12(S)-lipoxygenase activity
- Gene Name
- ALOX5
- Uniprot ID
- P09917
- Uniprot Name
- Polyunsaturated fatty acid 5-lipoxygenase
- Molecular Weight
- 77982.595 Da
References
- Charlier C, Michaux C: Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur J Med Chem. 2003 Jul-Aug;38(7-8):645-59. [Article]
- Kudo C, Kori M, Matsuzaki K, Yamai K, Nakajima A, Shibuya A, Niwa H, Kamisaki Y, Wada K: Diclofenac inhibits proliferation and differentiation of neural stem cells. Biochem Pharmacol. 2003 Jul 15;66(2):289-95. [Article]
- Whittle BJ: Cyclooxygenase and nitric oxide systems in the gut as therapeutic targets for safer anti-inflammatory drugs. Curr Opin Pharmacol. 2004 Dec;4(6):538-45. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration (PubMed:10455175, PubMed:10681567, PubMed:2925633). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (PubMed:10455175, PubMed:10681567). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:10358193, PubMed:11694541). Upon sterile inflammation, targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids such as arachidonate that is used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. Simultaneously, by compromising mitochondrial membrane integrity, promotes the release in circulation of potent damage-associated molecular pattern molecules that activate the innate immune response (PubMed:25082876). Plays a stem cell regulator role in the intestinal crypt. Within intracellular compartment mediates Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ICS). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ICS cells and tissue regeneration (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (PubMed:14998370). Independent of its catalytic activity, acts as a ligand for integrins (PubMed:18635536, PubMed:25398877). Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 (PubMed:18635536, PubMed:25398877). Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:25398877). Induces cell proliferation in an integrin-dependent manner (PubMed:18635536)
- Specific Function
- calcium ion binding
- Gene Name
- PLA2G2A
- Uniprot ID
- P14555
- Uniprot Name
- Phospholipase A2, membrane associated
- Molecular Weight
- 16082.525 Da
References
- Madanick RD, O'Loughlin CJ, Barkin JS: Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Dig Dis Sci. 2005 May;50(5):879-81. [Article]
- Singh N, Jabeen T, Sharma S, Somvanshi RK, Dey S, Srinivasan A, Singh TP: Specific binding of non-steroidal anti-inflammatory drugs (NSAIDs) to phospholipase A2: structure of the complex formed between phospholipase A2 and diclofenac at 2.7 A resolution. Acta Crystallogr D Biol Crystallogr. 2006 Apr;62(Pt 4):410-6. Epub 2006 Mar 18. [Article]
- Makela A, Kuusi T, Schroder T: Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. Scand J Clin Lab Invest. 1997 Aug;57(5):401-7. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain
- Specific Function
- hormone activity
- Gene Name
- TTR
- Uniprot ID
- P02766
- Uniprot Name
- Transthyretin
- Molecular Weight
- 15886.88 Da
References
- Miller SR, Sekijima Y, Kelly JW: Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab Invest. 2004 May;84(5):545-52. [Article]
- Almeida MR, Macedo B, Cardoso I, Alves I, Valencia G, Arsequell G, Planas A, Saraiva MJ: Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative. Biochem J. 2004 Jul 15;381(Pt 2):351-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Yamasaki K, Rahman MH, Tsutsumi Y, Maruyama T, Ahmed S, Kragh-Hansen U, Otagiri M: Circular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen. AAPS PharmSciTech. 2000 May 14;1(2):E12. [Article]
- Davies NM, Anderson KE: Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls. Clin Pharmacokinet. 1997 Sep;33(3):184-213. doi: 10.2165/00003088-199733030-00003. [Article]
Transporters
- 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
- Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. [Article]
- Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. [Article]
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685)
- Specific Function
- 15-hydroxyprostaglandin dehydrogenase (NAD+) activity
- Gene Name
- ABCC4
- Uniprot ID
- O15439
- Uniprot Name
- ATP-binding cassette sub-family C member 4
- Molecular Weight
- 149525.33 Da
References
- Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC1
- Uniprot ID
- P33527
- Uniprot Name
- Multidrug resistance-associated protein 1
- Molecular Weight
- 171589.5 Da
References
- Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. [Article]
- 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
- Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds (PubMed:10660625, PubMed:11907186, PubMed:15037815, PubMed:15102942, PubMed:15291761, PubMed:15576633, PubMed:17229912, PubMed:18501590, PubMed:26277985, PubMed:28027879). May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus (PubMed:12409283). Maybe also be involved in placental urate homeostasis (PubMed:17229912). Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates (PubMed:15037815, PubMed:17229912). Organic anion glutarate acts as conteranion for E1S renal uptake (PubMed:15037815, PubMed:17229912). Possible transport mode may also include DHEA-S/E1S exchange (PubMed:28027879). Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) (PubMed:17229912). Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion (PubMed:11907186). Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A (PubMed:10660625, PubMed:26277985). Mediates the unidirectional efflux of glutamate and aspartate (PubMed:28027879). Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S (PubMed:26277985)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A11
- Uniprot ID
- Q9NSA0
- Uniprot Name
- Solute carrier family 22 member 11
- Molecular Weight
- 59970.945 Da
References
- Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones L-thyroxine (T4), L-thyroxine sulfate (T4S), and 3,3',5'-triiodo-L-thyronine (reverse T3, rT3) at the plasma membrane (PubMed:12351693, PubMed:18566113, PubMed:19129463). Regulates T4 levels in different brain regions by transporting T4, and also by serving as an export pump for T4S, which is a source of T4 after hydrolysis by local sulfatases (PubMed:18566113). Increases the access of these substrates to the intracellular sites where they are metabolized by the deiodinases (PubMed:18566113). Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)), estrone-3-sulfate (E1S) and sulfobromophthalein (BSP) are transported with much lower efficiency (PubMed:12351693, PubMed:19129463). Transports T4 and E1S in a pH-insensitive manner (PubMed:19129463). Facilitates the transport of thyroid hormones across the blood-brain barrier and into glia and neuronal cells in the brain (PubMed:30296914)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1C1
- Uniprot ID
- Q9NYB5
- Uniprot Name
- Solute carrier organic anion transporter family member 1C1
- Molecular Weight
- 78695.625 Da
References
- Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW: Competitive inhibition of organic anion transporting polypeptide 1c1-mediated thyroxine transport by the fenamate class of nonsteroidal antiinflammatory drugs. Endocrinology. 2009 Feb;150(2):1025-32. doi: 10.1210/en.2008-0188. Epub 2008 Oct 9. [Article]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Karlgren M, Ahlin G, Bergstrom CA, Svensson R, Palm J, Artursson P: In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions. Pharm Res. 2012 Feb;29(2):411-26. doi: 10.1007/s11095-011-0564-9. Epub 2011 Aug 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
- Specific Function
- ABC-type bile acid transporter activity
- Gene Name
- ABCB11
- Uniprot ID
- O95342
- Uniprot Name
- Bile salt export pump
- Molecular Weight
- 146405.83 Da
References
- Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Pore-forming subunit of Nav1.4, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na+ ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:12766226, PubMed:15318338, PubMed:16890191, PubMed:17898326, PubMed:18690054, PubMed:19347921, PubMed:25707578, PubMed:26659129, PubMed:26700687, PubMed:29992740, PubMed:30190309). Highly expressed in skeletal muscles, Nav1.4 generates the action potential crucial for muscle contraction (PubMed:16890191, PubMed:19347921, PubMed:25707578, PubMed:26659129, PubMed:26700687)
- Specific Function
- voltage-gated sodium channel activity
- Gene Name
- SCN4A
- Uniprot ID
- P35499
- Uniprot Name
- Sodium channel protein type 4 subunit alpha
- Molecular Weight
- 208059.175 Da
References
- Yang YC, Kuo CC: An inactivation stabilizer of the Na+ channel acts as an opportunistic pore blocker modulated by external Na+. J Gen Physiol. 2005 May;125(5):465-81. Epub 2005 Apr 11. [Article]
- Voilley N: Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs). Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):71-9. [Article]
- Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB: Acid-induced pain and its modulation in humans. J Neurosci. 2004 Dec 1;24(48):10974-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Isoform 2 can also transport potassium, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 can also transport calcium ions. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear
- Specific Function
- ligand-gated sodium channel activity
- Gene Name
- ASIC1
- Uniprot ID
- P78348
- Uniprot Name
- Acid-sensing ion channel 1
- Molecular Weight
- 59908.915 Da
References
- Voilley N, de Weille J, Mamet J, Lazdunski M: Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci. 2001 Oct 15;21(20):8026-33. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability (PubMed:24277843, PubMed:28793216, PubMed:9836639). M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers (PubMed:10781098, PubMed:14534157, PubMed:32884139, PubMed:37857637, PubMed:9836639). The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs (PubMed:14534157, PubMed:28793216, PubMed:9836639). KCNQ2-KCNQ3 M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+) (PubMed:28793216). M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) (PubMed:28793216). Suppressed by activation of the muscarinic acetylcholine receptor CHRM1 (PubMed:10684873, PubMed:10713961)
- Specific Function
- ankyrin binding
- Gene Name
- KCNQ2
- Uniprot ID
- O43526
- Uniprot Name
- Potassium voltage-gated channel subfamily KQT member 2
- Molecular Weight
- 95846.575 Da
References
- Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. [Article]
- Xiong Q, Gao Z, Wang W, Li M: Activation of Kv7 (KCNQ) voltage-gated potassium channels by synthetic compounds. Trends Pharmacol Sci. 2008 Feb;29(2):99-107. doi: 10.1016/j.tips.2007.11.010. Epub 2008 Jan 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability (PubMed:16319223, PubMed:27564677, PubMed:28793216, PubMed:9872318). M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers (PubMed:14534157, PubMed:16319223, PubMed:27564677, PubMed:9872318). The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs (PubMed:14534157, PubMed:16319223, PubMed:28793216). M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+) (PubMed:28793216). M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) (PubMed:28793216). Suppressed by activation of M1 muscarinic acetylcholine receptors (PubMed:10713961). KCNQ3 also associates with KCNQ5 to form a functional channel in vitro and may also contribute to the M-current in brain (PubMed:11159685)
- Specific Function
- calmodulin binding
- Gene Name
- KCNQ3
- Uniprot ID
- O43525
- Uniprot Name
- Potassium voltage-gated channel subfamily KQT member 3
- Molecular Weight
- 96741.515 Da
References
- Xiong Q, Gao Z, Wang W, Li M: Activation of Kv7 (KCNQ) voltage-gated potassium channels by synthetic compounds. Trends Pharmacol Sci. 2008 Feb;29(2):99-107. doi: 10.1016/j.tips.2007.11.010. Epub 2008 Jan 18. [Article]
- Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- 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
- Sanchez-Covarrubias L, Slosky LM, Thompson BJ, Zhang Y, Laracuente ML, DeMarco KM, Ronaldson PT, Davis TP: P-glycoprotein modulates morphine uptake into the CNS: a role for the non-steroidal anti-inflammatory drug diclofenac. PLoS One. 2014 Feb 10;9(2):e88516. doi: 10.1371/journal.pone.0088516. eCollection 2014. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 18:18