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Identification
- Summary
Eltrombopag is a thrombopoietin receptor agonist used to treat thrombocytopenia or aplastic anemia associated with various etiologies.
- Brand Names
- Alvaiz, Promacta
- Generic Name
- Eltrombopag
- DrugBank Accession Number
- DB06210
- Background
Eltrombopag is used to treat low blood platelet counts in adults with chronic immune (idiopathic) thrombocytopenia (ITP), when certain other medicines, or surgery to remove the spleen, have not worked well enough. ITP is a condition that may cause unusual bruising or bleeding due to an abnormally low number of platelets in the blood. Eltrombopag has also been recently approved (late 2012) for the treatment of thrombocytopenia (low blood platelet counts) in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Eltrombopag (DB06210)
- Weight
- Average: 442.4666
Monoisotopic: 442.164105212 - Chemical Formula
- C25H22N4O4
- Synonyms
- Eltrombopag
- Eltrombopagum
- External IDs
- SB 497115
- SB-497115
- SB497115
Pharmacology
- Indication
Thrombopoietin receptor agonists are pharmaceutical agents that stimulate platelet production in the bone marrow. In this, they differ from the previously discussed agents that act by attempting to curtail platelet destruction.
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 Chronic immune thrombocytopenia •••••••••••• ••••••••• •••• •• ••••••••• •••••••••••• •••••••• •• ••••• ••••••••• Treatment of Severe aplastic anemia (saa) •••••••••••• •••••••• ••••••••••••••••• •••••••• •••••••••••• •••••••• •• • •••••••• ••••••••• Adjunct therapy in treatment of Severe aplastic anemia (saa) •••••••••••• ••••••••• ••••• Treatment of Thrombocytopenia •••••••••••• •••••••••• •••••••••• ••••••• ••••••••• • ••••• ••••• ••••••••• Treatment of Thrombocytopenia •••••••••••• •••••••••••• •••••••• •• ••••• ••••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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Not Available
- Mechanism of action
Eltrombopag is an orally bioavailable, small-molecule TPO-receptor agonist that interacts with the transmembrane domain of the human TPO-receptor. Eltrombopag is a stimulator of STAT and JAK phosphorylation. Unlike recombinant TPO or romiplostim, Eltrombopag does not activate the AKT pathway in any way. It should be noted that when given to patients with aplastic anemia, other lineages besides platelet count were increased, suggesting that either eltrombopag enhanced the effect of TPO in vivo; or there is a yet uncovered mechanism of action at work.
Target Actions Organism AThrombopoietin receptor agonistHumans - Absorption
Peak absorption of Eltrombopag occurs around 2-6 hours following oral administration, and the total oral absorption of drug-related material following a 75 mg dose was estimated to be at least 52%.
- Volume of distribution
Based on a radiolabel study, the concentration of eltrombopag in blood cells is approximately 50% to 79% of plasma concentrations.
- Protein binding
Eltrombopag is highly protein bound (>99%).
- Metabolism
Eltrombopag is predominantly through pathways including cleavage, oxidation, and conjugation with glucuronic acid, glutathione, or cysteine. In vitro studies suggest that CYP1A2 and CYP2C8 are responsible for the oxidative metabolism of eltrombopag. UGT1A1 and UGT1A3 are responsible for the glucuronidation of eltrombopag.
- Route of elimination
Eltrombopag is eliminated primarily via the feces (59%), along with 31% being renally excreted.
- Half-life
About 21-32 hours in healthy patients. About 26-35 hours in patients with idiopathic thrombocytopenic purpura.
- Clearance
Not Available
- Adverse Effects
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Eltrombopag may cause hepatotoxicity, especially if administered in combination with interferon and ribavirin in patients with chronic hepatitis C (may increase the risk of hepatic decompensation).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Coagulation factor V Factor V Leiden (A;A) / (A;G) A allele ADR Directly Studied Patients who carry this polymorphism in F5 are associated with an increased risk of thromboembolism when treated with eltrombopag. Details Antithrombin-III --- (T;T) C > T ADR Directly Studied Patients who carry this polymorphism in SERPINC1 are associated with antithrombin III deficiency and an increased risk of thromboembolism when treated with eltrombopag. Details
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir The metabolism of Abacavir can be decreased when combined with Eltrombopag. Abametapir The serum concentration of Eltrombopag can be increased when it is combined with Abametapir. Abatacept The metabolism of Eltrombopag can be increased when combined with Abatacept. Abemaciclib Eltrombopag may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Abiraterone The serum concentration of Eltrombopag can be increased when it is combined with Abiraterone. - Food Interactions
- Avoid multivalent ions. Polyvalent cations in food or supplements will be chelated by eltrombopag; therefore, they should be separated by 4 hours before or 2 hours after taking eltrombopag.
- Take on an empty stomach. Separate the administration of eltrombopag from food by at least 1 hour before and 2 hours after eating.
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 Eltrombopag choline F9G8XE24IB 2336813-25-1 XSHFVAAXJHNDKZ-OUFJFOJPSA-M Eltrombopag olamine 4U07F515LG 496775-62-3 PLILLUUXAVKBPY-SBIAVEDLSA-N - Product Images
- International/Other Brands
- Promacta / Revolade
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alvaiz Tablet, film coated 18 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2024-02-13 Not applicable US 
Alvaiz Tablet, film coated 54 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2024-02-13 Not applicable US Alvaiz Tablet, film coated 9 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2024-02-13 Not applicable US Alvaiz Tablet, film coated 36 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2024-02-13 Not applicable US Promacta Tablet, film coated 100 mg/1 Oral Glaxosmithkline Inc 2014-03-10 2016-11-28 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-eltrombopag Tablet 50 mg Oral Apotex Corporation 2023-05-23 Not applicable Canada 
Apo-eltrombopag Tablet 25 mg Oral Apotex Corporation 2023-05-23 Not applicable Canada Teva-eltrombopag Tablet 50 mg Oral Teva Italia S.R.L. Not applicable Not applicable Canada Teva-eltrombopag Tablet 25 mg Oral Teva Italia S.R.L. Not applicable Not applicable Canada
Categories
- ATC Codes
- B02BX05 — Eltrombopag
- Drug Categories
- Acids, Carbocyclic
- BCRP/ABCG2 Inhibitors
- Benzene Derivatives
- Blood and Blood Forming Organs
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (moderate)
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Hematinics
- Hemostatics
- Increased Megakaryocyte Maturation
- Increased Platelet Production
- OATP1B1/SLCO1B1 Inhibitors
- Organic Anion Transporting Polypeptide 1B1 Inhibitors
- Thrombopoietin Receptor Agonist
- Thrombopoietin Receptor Agonists
- UGT1A1 Inhibitors
- UGT1A1 Substrates
- UGT1A3 Inhibitors
- UGT1A3 substrates
- UGT1A4 Inhibitors
- UGT1A6 Inhibitors
- UGT1A9 Inhibitors
- UGT2B15 Inhibitors
- UGT2B7 Inhibitors
- 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
- Benzoic acids / o-Xylenes / Phenylhydrazines / Benzoyl derivatives / 1-hydroxy-4-unsubstituted benzenoids / Pyrazolones / Monocarboxylic acids and derivatives / Hydrazones / Carboxylic acids / Azacyclic compounds show 4 more
- Substituents
- 1-hydroxy-4-unsubstituted benzenoid / Aromatic heteromonocyclic compound / Azacycle / Benzoic acid / Benzoic acid or derivatives / Benzoyl / Biphenyl / Carbonyl group / Carboxylic acid / Carboxylic acid derivative show 16 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- pyrazoles, hydrazines, benzoic acids (CHEBI:85010)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- S56D65XJ9G
- CAS number
- 496775-61-2
- InChI Key
- XDXWLKQMMKQXPV-QYQHSDTDSA-N
- InChI
- InChI=1S/C25H22N4O4/c1-14-10-11-19(12-15(14)2)29-24(31)22(16(3)28-29)27-26-21-9-5-8-20(23(21)30)17-6-4-7-18(13-17)25(32)33/h4-13,26,30H,1-3H3,(H,32,33)/b27-22-
- IUPAC Name
- 3'-{2-[(4Z)-1-(3,4-dimethylphenyl)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-ylidene]hydrazin-1-yl}-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid
- SMILES
- CC1=NN(C(=O)\C1=N/NC1=CC=CC(C2=CC=CC(=C2)C(O)=O)=C1O)C1=CC=C(C)C(C)=C1
References
- Synthesis Reference
http://doc.sciencenet.cn/upload/file/2011531154034454.pdf
- General References
- Zekry A, Freiman J: Eltrombopag: Is this "24 karat gold platelet" treatment for thrombocytopenia in cirrhosis associated with hepatitis C? Hepatology. 2008 Apr;47(4):1418-21. doi: 10.1002/hep.22300. [Article]
- Mondelli MU: Eltrombopag: an effective remedy for thrombocytopaenia? J Hepatol. 2008 Jun;48(6):1030-2. doi: 10.1016/j.jhep.2008.03.008. Epub 2008 Mar 31. [Article]
- Tarantino MD, Fogarty P, Mayer B, Vasey SY, Brainsky A: Efficacy of eltrombopag in management of bleeding symptoms associated with chronic immune thrombocytopenia. Blood Coagul Fibrinolysis. 2013 Apr;24(3):284-96. doi: 10.1097/MBC.0b013e32835fac99. [Article]
- Kiang TK, Ensom MH, Chang TK: UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol Ther. 2005 Apr;106(1):97-132. Epub 2005 Jan 12. [Article]
- Deng Y, Madatian A, Wire MB, Bowen C, Park JW, Williams D, Peng B, Schubert E, Gorycki F, Levy M, Gorycki PD: Metabolism and disposition of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, in healthy human subjects. Drug Metab Dispos. 2011 Sep;39(9):1734-46. doi: 10.1124/dmd.111.040170. Epub 2011 Jun 6. [Article]
- Kuter DJ: The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013 Jul;98(1):10-23. doi: 10.1007/s12185-013-1382-0. Epub 2013 Jul 3. [Article]
- Eltrombopag [File]
- External Links
- KEGG Drug
- D03978
- PubChem Compound
- 9846180
- PubChem Substance
- 175427059
- ChemSpider
- 19879943
- 711942
- ChEBI
- 85010
- ChEMBL
- CHEMBL461101
- ZINC
- ZINC000011679756
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Eltrombopag
- FDA label
- Download (197 KB)
- MSDS
- Download (33.7 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 Available Not Available Thrombocytopenia 1 somestatus stop reason just information to hide Not Available Completed Not Available Connective Tissue Disorders / Refractory Thrombocytopenia 1 somestatus stop reason just information to hide Not Available Completed Not Available Hepatitis C Virus (HCV) Infection 2 somestatus stop reason just information to hide Not Available Completed Not Available Immune Thrombocytopenia (ITP) 2 somestatus stop reason just information to hide Not Available Completed Not Available Purpura, Thrombocytopaenic, Idiopathic 3 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 18 mg/1 Tablet, film coated Oral 36 mg/1 Tablet, film coated Oral 54 mg/1 Tablet, film coated Oral 9 mg/1 Powder, for suspension Oral 12.5 mg/1 Powder, for suspension Oral 25 mg/1 Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 12.5 mg/1 Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 50 mg/1 Tablet, film coated Oral 75 mg/1 Tablet, film coated Oral 31.9 MG Tablet, film coated Oral 63.8 MG Powder, for suspension Oral 25 MG Tablet Oral 12.5 mg Tablet Oral 25 mg Tablet Oral 50 mg Tablet Oral 75 mg Tablet, film coated Oral 75 MG Tablet, film coated Oral 12.5 mg Tablet, film coated Oral 25 mg Tablet, film coated Oral 50 mg Tablet, coated Oral 25 mg Tablet, coated Oral 50 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8052995 Yes 2011-11-08 2028-02-01 US US6280959 Yes 2001-08-28 2019-04-30 US US7790704 Yes 2010-09-07 2021-11-24 US US7452874 Yes 2008-11-18 2021-11-24 US US7473686 Yes 2009-01-06 2021-11-24 US US7160870 Yes 2007-01-09 2023-05-20 US US7795293 Yes 2010-09-14 2023-11-21 US US7547719 Yes 2009-06-16 2026-01-13 US US7332481 Yes 2008-02-19 2021-11-24 US US8062665 Yes 2011-11-22 2028-02-01 US US8052994 Yes 2011-11-08 2028-02-01 US US8071129 Yes 2011-12-06 2028-02-01 US US8052993 Yes 2011-11-08 2028-02-01 US US8828430 Yes 2014-09-09 2028-02-01 US US11072586 No 2018-11-05 2038-11-05 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Eltrombopag olamine is practically insoluble in aqueous buffer across a pH range of 1 to 7.4, and is sparingly soluble in water. FDA Label - Predicted Properties
Property Value Source Water Solubility 0.0103 mg/mL ALOGPS logP 4.02 ALOGPS logP 6.03 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 3.97 Chemaxon pKa (Strongest Basic) -0.12 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 114.59 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 126.48 m3·mol-1 Chemaxon Polarizability 47.7 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.6946 Blood Brain Barrier - 0.6616 Caco-2 permeable - 0.5811 P-glycoprotein substrate Non-substrate 0.6578 P-glycoprotein inhibitor I Non-inhibitor 0.8297 P-glycoprotein inhibitor II Non-inhibitor 0.9187 Renal organic cation transporter Non-inhibitor 0.944 CYP450 2C9 substrate Non-substrate 0.5991 CYP450 2D6 substrate Non-substrate 0.8495 CYP450 3A4 substrate Substrate 0.5424 CYP450 1A2 substrate Non-inhibitor 0.8173 CYP450 2C9 inhibitor Inhibitor 0.6357 CYP450 2D6 inhibitor Non-inhibitor 0.8982 CYP450 2C19 inhibitor Non-inhibitor 0.7625 CYP450 3A4 inhibitor Non-inhibitor 0.7595 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6304 Ames test Non AMES toxic 0.5993 Carcinogenicity Non-carcinogens 0.5481 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.1796 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9862 hERG inhibition (predictor II) Non-inhibitor 0.6936
Spectra
- Mass Spec (NIST)
- Download (91.2 KB)
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-2811240825c78197a010 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0005-0069300000-2ecec5b62201b8929322 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0007-0269100000-efa7ebb329d0072f9671 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004l-0003900000-59c65fcf0a32d9144561 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-052f-6953200000-1f0b1a8859b28219f3be Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0032-3958200000-c4d6c0a88513f511d53f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 204.24486 predictedDeepCCS 1.0 (2019) [M+H]+ 206.64043 predictedDeepCCS 1.0 (2019) [M+Na]+ 212.55296 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for thrombopoietin that acts as a primary regulator of megakaryopoiesis and platelet production. May represent a regulatory molecule specific for TPO-R-dependent immune responses
- Specific Function
- thrombopoietin receptor activity
- Gene Name
- MPL
- Uniprot ID
- P40238
- Uniprot Name
- Thrombopoietin receptor
- Molecular Weight
- 71244.08 Da
References
- Kuter DJ: Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. Annu Rev Med. 2009;60:193-206. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
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, 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation 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 losartan, 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:18004212, PubMed:20610558)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
Transporters
- 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
- Kuter DJ: The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013 Jul;98(1):10-23. doi: 10.1007/s12185-013-1382-0. Epub 2013 Jul 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
Drug created at March 19, 2008 16:17 / Updated at August 26, 2024 19:23