Azilsartan medoxomil
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Identification
- Summary
Azilsartan medoxomil is an angiotensin II receptor blocker used to treat hypertension alone or in combination with other antihypertensive agents, such as chlorthalidone.
- Brand Names
- Edarbi, Edarbyclor
- Generic Name
- Azilsartan medoxomil
- DrugBank Accession Number
- DB08822
- Background
Azilsartan medoxomil is a prodrug that is broken down to azilsartan, which belongs in the angiotensin-receptor blocking (ARB) drug class. It is a selective AT1 subtype angiotensin II receptor antagonist. Azilsartan medoxomil is a relatively recently-developed antihypertensive drug that was first approved by the FDA in February 2011.1 Many guidelines recommend the use of ARBs as first-line therapy when initiating antihypertensive therapy and indicate that the clinical efficacy of ARBs is comparable to angiotensin-converting enzyme (ACE) inhibitors that are also used as first-line treatment for hypertension.3
Azilsartan medoxomil is marketed under the brand name Edarbi. It is used to treat hypertension as monotherapy or in combination with other antihypertensive drugs. It is also available in a combination product with chlorthalidone. As hypertension is a major risk factor for cardiovascular disease,1 early management of hypertension has several implications on patients' survival rate and quality of life in the future. Lowering blood pressure is associated with a reduced risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.6 Azilsartan medoxomil is thus speculated to lower mortality rates and the onset of cardiovascular disease. Although there is no clinical significance yet determined, azilsartan medoxomil may have potential off-label uses in patients with a history of myocardial infarction or heart failure.3
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 568.5336
Monoisotopic: 568.159413764 - Chemical Formula
- C30H24N4O8
- Synonyms
- Azilsartan
- Azilsartan médoxomil
- Azilsartan medoxomil
- Azilsartán medoxomilo
- Azilsartanum medoxomilum
- External IDs
- TAK 491
- TAK-491
- TAK-536
Pharmacology
- Indication
Azilsartan medoxomil is indicated for the treatment of hypertension to lower blood pressure in patients over 18 years of age. It may be used either alone or in combination with other antihypertensive agents. Some antihypertensive drugs have lesser effects on blood pressure in black patients.6
Azilsartan medoxomil is available as a fixed-dose combination product with chlorthalidone, which is indicated for the treatment of hypertension in patients whose hose blood pressure is not adequately controlled on monotherapy. It may be used as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals.7
Azilsartan medoxomil belongs to the angiotensin-receptor blocking (ARB) class of drugs, which are used to decrease the progression of moderate-to-severe albuminuria and prevent the recurrence of atrial fibrillation as off-label uses in patients with diabetes mellitus and hypertension.3
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 Management of Albuminuria ••• ••••• ••••• ••••••••• •••• ••••• •••••••• •••••••••••••• •••••• Prevention of Atrial fibrillation ••• ••••• ••••• ••••••••• •••• ••••• •••••••• •••••••••••••• •••••• Used in combination to manage Hypertension Combination Product in combination with: Chlorthalidone (DB00310) •••••••••••• •••••••••• •••••••• •• ••••••••••• •••••• Management of Hypertension •••••••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Pharmacodynamic effects of azilsartan medoxomil are mediated by its active metabolite, azilsartan. Azilsartan inhibits the pressor effects of an angiotensin II infusion in a dose-related manner.1 At a single 32 mg dose, azilsartan inhibited the maximal pressor effect by approximately 90% at peak plasma concentrations and by 60% at 24 hours after administration. In healthy subjects receiving single and repeated doses of azilsartan medoxomil, plasma angiotensin I and II concentrations and plasma renin activity increased, while plasma aldosterone concentrations decreased.6 Like other ARBs, azilsartan causes dose-dependent decrease in peripheral resistance and decreases smooth muscle vascular tone.4 As azilsartan blocks the angiotensin II receptor, the negative regulatory feedback of angiotensin II on renin secretion is inhibited; however, the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the blood pressure-lowering effect of azilsartan. Blood pressure-lowering effects of antihypertensive agents can be reduced in patients of African descent.6 However, there are no recommended dosage adjustment of azilsartan on the basis of a patient’s sex, race, or degree of renal or hepatic impairment.5
Azilsartan medoxomil has negligible effects on serum potassium or sodium levels. Azilsartan does not affect the biosynthesis of angiotensin II nor bradykinin levels. It also does not bind to any ion channels that are involved in cardiovascular regulation.6
- Mechanism of action
The renin-angiotensin-aldosterone system regulates blood pressure. Angiotensin II is a peptide hormone that is a principal pressor agent in the renin-angiotensin-aldosterone system.1 It is a potent, direct vasoconstrictor that binds to the angiotensin II type 1 receptor (AT1 receptor) to stimulate the synthesis and release of aldosterone and promote cardiac stimulation. Angiotensin II promotes renal tubular reabsorption of sodium, resulting in water retention.1,6 It also inhibits further secretion of renin. AT1 receptors are highly expressed in vascular smooth muscle and the adrenal gland.3
Azilsartan medoxomil is a prodrug that is hydrolyzed to its active metabolite, azilsartan, in the gastrointestinal tract following oral administration. Azilsartan selectively binds to AT1 receptors as an antagonist, blocking vasoconstrictor and aldosterone-secreting effects of angiotensin II. Azilsartan has more than a 10,000-fold greater affinity for the AT1 receptor than for the AT2 receptor, which is predominantly involved in cardiovascular homeostasis.6 Azilsartan appears to dissociate from AT1 receptors much more slowly than other ARBs,2 which explains its longer duration of action when compared to other ARBs.4
Target Actions Organism AType-1 angiotensin II receptor antagonistHumans - Absorption
During absorption, azilsartan medoxomil is hydrolyzed to azilsartan. The parent drug is not detectable in plasma after oral administration. The absolute bioavailability of azilsartan is estimated to be 60%. Tmax ranges from 1.5 to three hours. Steady-state levels of azilsartan are achieved within five days, and no accumulation in plasma occurs with repeated once-daily dosing.6
- Volume of distribution
The volume of distribution of azilsartan is approximately 16 L. In rats, a minimal amount of radiolabelled drug crossed the blood-brain barrier. Azilsartan crossed the placental barrier in pregnant rats and was distributed to the fetus.6
- Protein binding
Azilsartan is >99% bound to human plasma proteins, mainly serum albumin. Protein binding is constant at azilsartan plasma concentrations well above the range achieved with recommended doses.6
- Metabolism
After azilsartan medoxomil is hydrolyzed into its active metabolite, azilsartan is metabolized to two primary metabolites, which are pharmacologically inactive. The major metabolite in plasma is metabolite M-II, which is formed via O-dealkylation mediated by CYP2C9. The minor metabolite is metabolite M-I, which is formed via decarboxylation mediated by CYP2C8 and CYP2B6. MII has approximately 50% systemic exposure of azilsartan, and MI has less than 1% systemic exposure of azilsartan.5,6
Hover over products below to view reaction partners
- Route of elimination
Following oral administration of 14C-labeled azilsartan medoxomil, approximately 55% of radioactivity was recovered in feces and approximately 42% in urine. Of the recovered dose in urine, about 15% was excreted as azilsartan.6
- Half-life
The elimination half-life of azilsartan is approximately 11 hours.6
- Clearance
Renal clearance of azilsartan is approximately 2.3 mL/min.6
- 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
No maximum toxic doses have been established yet for azilsartan.3 There is limited human data available related to azilsartan medoxomil overdosage. In clinical trials, healthy subjects tolerated once-daily doses up to 320 mg of azilsartan medoxomil well. In the event of drug overdose, supportive measures should be initiated as azilsartan is not dialyzable.6
Azilsartan is a teratogenic agent with a risk of congenital abnormalities. Azilsartan and other ARB drugs are considered fetotoxic during the second and third trimesters.3,6
- Pathways
- Not Available
- 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 softwareAbaloparatide The risk or severity of adverse effects can be increased when Abaloparatide is combined with Azilsartan medoxomil. Acebutolol Acebutolol may increase the hypotensive activities of Azilsartan medoxomil. Aceclofenac The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Azilsartan medoxomil is combined with Aceclofenac. Acemetacin The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Azilsartan medoxomil is combined with Acemetacin. Acetylsalicylic acid The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Azilsartan medoxomil is combined with Acetylsalicylic acid. - Food Interactions
- Take with or without food. Food does not affect the bioavailability.
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 Azilsartan medoxomil potassium WEC6I2K1FC 863031-24-7 IHWFKDWIUSZLCJ-UHFFFAOYSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Edarbi Tablet 40 mg Oral Takeda Pharma A/S 2020-12-16 Not applicable EU Edarbi Tablet 20 mg Oral Takeda Pharma A/S 2020-12-16 Not applicable EU Edarbi Tablet 80 mg Oral Takeda Pharma A/S 2020-12-16 Not applicable EU Edarbi Tablet 80 mg Oral Takeda Pharma A/S 2020-12-16 Not applicable EU Edarbi Tablet 40 mg Oral Takeda Pharma A/S 2020-12-16 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Edarbyclor Azilsartan medoxomil potassium (40 mg/1) + Chlorthalidone (25 mg/1) Tablet Oral Azurity Pharmaceuticals, Inc. (formerly Arbor Pharmaceuticals) 2013-02-01 Not applicable US Edarbyclor Azilsartan medoxomil potassium (40 mg) + Chlorthalidone (25 mg) Tablet Oral Bausch Health, Canada Inc. 2013-03-21 Not applicable Canada Edarbyclor Azilsartan medoxomil (40 mg/1) + Chlorthalidone (25 mg/1) Tablet Oral Takeda Italia S.P.A. 2011-12-23 2018-05-01 US Edarbyclor Azilsartan medoxomil potassium (40 mg/1) + Chlorthalidone (12.5 mg/1) Tablet Oral Azurity Pharmaceuticals, Inc. (formerly Arbor Pharmaceuticals) 2013-02-01 Not applicable US Edarbyclor Azilsartan medoxomil potassium (40 mg) + Chlorthalidone (12.5 mg) Tablet Oral Bausch Health, Canada Inc. 2013-03-21 Not applicable Canada
Categories
- ATC Codes
- C09CA09 — Azilsartan medoxomil
- C09CA — Angiotensin II receptor blockers (ARBs), plain
- C09C — ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), PLAIN
- C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- Agents Acting on the Renin-Angiotensin System
- Agents causing angioedema
- Agents causing hyperkalemia
- Angiotensin 2 Receptor Blocker
- Angiotensin II receptor antagonists
- Angiotensin II receptor blockers (ARBs) and diuretics
- Angiotensin II receptor blockers (ARBs), plain
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Antihypertensive Agents
- Antihypertensive Agents Indicated for Hypertension
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 Substrates
- Decreased Blood Pressure
- Heterocyclic Compounds, Fused-Ring
- Hypotensive Agents
- Oxazoles
- P-glycoprotein inhibitors
- Teratogens
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Biphenyls and derivatives
- Direct Parent
- Biphenyls and derivatives
- Alternative Parents
- Phenyloxadiazoles / Benzimidazoles / Alkyl aryl ethers / N-substituted imidazoles / Carbonic acid diesters / Vinylogous amides / Heteroaromatic compounds / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives show 5 more
- Substituents
- 1,2,4-oxadiazole / Alkyl aryl ether / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzimidazole / Biphenyl / Carbonic acid diester / Carboxylic acid derivative / Carboxylic acid ester show 17 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- aromatic ether, carboxylic ester, dioxolane, cyclic carbonate ester, benzimidazoles, 1,2,4-oxadiazole (CHEBI:68845)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- LL0G25K7I2
- CAS number
- 863031-21-4
- InChI Key
- QJFSABGVXDWMIW-UHFFFAOYSA-N
- InChI
- InChI=1S/C30H24N4O8/c1-3-38-28-31-23-10-6-9-22(27(35)39-16-24-17(2)40-30(37)41-24)25(23)34(28)15-18-11-13-19(14-12-18)20-7-4-5-8-21(20)26-32-29(36)42-33-26/h4-14H,3,15-16H2,1-2H3,(H,32,33,36)
- IUPAC Name
- (5-methyl-2-oxo-2H-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl]methyl}-1H-1,3-benzodiazole-7-carboxylate
- SMILES
- CCOC1=NC2=C(N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NOC(=O)N1)C(=CC=C2)C(=O)OCC1=C(C)OC(=O)O1
References
- Synthesis Reference
Kohara Y, Kubo K, Imamiya E, Wada T, Inada Y, Naka T: Synthesis and angiotensin II receptor antagonistic activities of benzimidazole derivatives bearing acidic heterocycles as novel tetrazole bioisosteres. J Med Chem. 1996 Dec 20;39(26):5228-35.
- General References
- Jones JD, Jackson SH, Agboton C, Martin TS: Azilsartan Medoxomil (Edarbi): The Eighth Angiotensin II Receptor Blocker. P T. 2011 Oct;36(10):634-40. [Article]
- Kurtz TW, Kajiya T: Differential pharmacology and benefit/risk of azilsartan compared to other sartans. Vasc Health Risk Manag. 2012;8:133-43. doi: 10.2147/VHRM.S22595. Epub 2012 Feb 28. [Article]
- Hardin MD, Jacobs TF: Azilsartan . [Article]
- Pradhan A, Tiwari A, Sethi R: Azilsartan: Current Evidence and Perspectives in Management of Hypertension. Int J Hypertens. 2019 Nov 3;2019:1824621. doi: 10.1155/2019/1824621. eCollection 2019. [Article]
- De Caterina AR, Harper AR, Cuculi F: Critical evaluation of the efficacy and tolerability of azilsartan. Vasc Health Risk Manag. 2012;8:299-305. doi: 10.2147/VHRM.S22589. Epub 2012 May 14. [Article]
- FDA Approved Drug Products: Edarbi (azilsartan medoxomil) oral tablets [Link]
- FDA Approved Drug Products: EDARBYCLOR (azilsartan medoxomil and chlorthalidone) tablets, for oral use [Link]
- FDA Approved Drug Products: Edarbi (azilsartan medoxomil) tablets, for oral use (Jan 2024) [Link]
- External Links
- Human Metabolome Database
- HMDB0248803
- KEGG Drug
- D08865
- PubChem Compound
- 11238823
- PubChem Substance
- 175427104
- ChemSpider
- 9413866
- 1091643
- ChEBI
- 68845
- ChEMBL
- CHEMBL2028661
- ZINC
- ZINC000014210642
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Azilsartan
- FDA label
- Download (381 KB)
- MSDS
- Download (34.9 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 Completed Not Available Chronic Stable Angina Pectoris / Diabetes Mellitus / Hypertension Arterial 1 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / COVID / Hypertension 1 somestatus stop reason just information to hide Not Available Completed Not Available Hypertension 5 somestatus stop reason just information to hide Not Available Completed Not Available Hypertension, Essential Hypertension 1 somestatus stop reason just information to hide Not Available Completed Treatment Hypertension 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 40 mg/1 Tablet Oral 42.680 mg Tablet Oral 80 mg/1 Tablet Oral 40 mg Tablet Oral 80 mg Tablet Oral 20 MG Tablet, coated Oral Tablet Oral Tablet, film coated Tablet Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9169238 No 2015-10-27 2030-02-25 US US7572920 No 2009-08-11 2025-01-07 US US9066936 No 2015-06-30 2028-03-26 US US7157584 No 2007-01-02 2025-05-22 US US9387249 No 2016-07-12 2031-07-01 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility <1 mg/mL https://www.selleck.cn/msds/MSDS_S3057.pdf - Predicted Properties
Property Value Source Water Solubility 0.00703 mg/mL ALOGPS logP 4.94 ALOGPS logP 6.03 Chemaxon logS -4.9 ALOGPS pKa (Strongest Acidic) 5.91 Chemaxon pKa (Strongest Basic) 1.48 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 139.57 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 149.52 m3·mol-1 Chemaxon Polarizability 57.4 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.915 Caco-2 permeable - 0.5843 P-glycoprotein substrate Substrate 0.5619 P-glycoprotein inhibitor I Non-inhibitor 0.5061 P-glycoprotein inhibitor II Non-inhibitor 0.7217 Renal organic cation transporter Non-inhibitor 0.8851 CYP450 2C9 substrate Non-substrate 0.834 CYP450 2D6 substrate Non-substrate 0.8338 CYP450 3A4 substrate Substrate 0.5128 CYP450 1A2 substrate Non-inhibitor 0.7445 CYP450 2C9 inhibitor Inhibitor 0.5531 CYP450 2D6 inhibitor Non-inhibitor 0.8779 CYP450 2C19 inhibitor Inhibitor 0.5915 CYP450 3A4 inhibitor Inhibitor 0.8507 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.594 Ames test Non AMES toxic 0.5227 Carcinogenicity Non-carcinogens 0.7059 Biodegradation Not ready biodegradable 0.9962 Rat acute toxicity 2.5320 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8853 hERG inhibition (predictor II) Non-inhibitor 0.6952
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 252.9994528 predictedDarkChem Lite v0.1.0 [M-H]- 221.51048 predictedDeepCCS 1.0 (2019) [M+H]+ 253.5634528 predictedDarkChem Lite v0.1.0 [M+H]+ 223.80333 predictedDeepCCS 1.0 (2019) [M+Na]+ 253.5769528 predictedDarkChem Lite v0.1.0 [M+Na]+ 229.71587 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney (PubMed:15611106, PubMed:1567413, PubMed:25913193, PubMed:26420482, PubMed:30639100, PubMed:32079768, PubMed:8987975). The activated receptor in turn couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C (PubMed:15611106)
- Specific Function
- angiotensin type I receptor activity
- Gene Name
- AGTR1
- Uniprot ID
- P30556
- Uniprot Name
- Type-1 angiotensin II receptor
- Molecular Weight
- 41060.53 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Miura S, Matsuo Y, Nakayama A, Tomita S, Suematsu Y, Saku K: Ability of the new AT1 receptor blocker azilsartan to block angiotensin II-induced AT1 receptor activation after wash-out. J Renin Angiotensin Aldosterone Syst. 2014 Mar;15(1):7-12. doi: 10.1177/1470320313482170. Epub 2013 Apr 5. [Article]
- Jones JD, Jackson SH, Agboton C, Martin TS: Azilsartan Medoxomil (Edarbi): The Eighth Angiotensin II Receptor Blocker. P T. 2011 Oct;36(10):634-40. [Article]
- Hardin MD, Jacobs TF: Azilsartan . [Article]
- FDA Approved Drug Products: Edarbi (azilsartan medoxomil) oral tablets [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- De Caterina AR, Harper AR, Cuculi F: Critical evaluation of the efficacy and tolerability of azilsartan. Vasc Health Risk Manag. 2012;8:299-305. doi: 10.2147/VHRM.S22589. Epub 2012 May 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- De Caterina AR, Harper AR, Cuculi F: Critical evaluation of the efficacy and tolerability of azilsartan. Vasc Health Risk Manag. 2012;8:299-305. doi: 10.2147/VHRM.S22589. Epub 2012 May 14. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- 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
- FDA Approved Drug Products: Edarbi (azilsartan medoxomil) oral tablets [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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
- De Caterina AR, Harper AR, Cuculi F: Critical evaluation of the efficacy and tolerability of azilsartan. Vasc Health Risk Manag. 2012;8:299-305. doi: 10.2147/VHRM.S22589. Epub 2012 May 14. [Article]
Drug created at December 21, 2012 17:01 / Updated at January 24, 2024 05:40