Mifepristone
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Identification
- Summary
Mifepristone is a cortisol receptor blocker used to treat Cushing's syndrome, and to terminate pregnancies up to 70 days gestation.
- Brand Names
- Korlym, Mifegymiso
- Generic Name
- Mifepristone
- DrugBank Accession Number
- DB00834
- Background
Mifepristone is a progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary cushing syndrome. The two marketed forms of mifepristone are Mifeprex® (mifepristone 200mg) and Korlym™ (mifepristone 300mg). Currently under investigation for use in psychotic depression (phase 3 trials).
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 429.5937
Monoisotopic: 429.266779369 - Chemical Formula
- C29H35NO2
- Synonyms
- Mifepriston
- Mifepristona
- Mifépristone
- Mifepristone
- Mifepristonum
- External IDs
- RU 38486
- RU 486
- RU-38486
- RU-486
- RU486
Pharmacology
- Indication
For the medical termination of intrauterine pregnancy through 49 days' pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have had unsuccessful surgery.
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 Hyperglycemia •••••••••••• - Associated Therapies
- 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
Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol.
- Mechanism of action
The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results.
In the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels.
Target Actions Organism AProgesterone receptor antagonistHumans AGlucocorticoid receptor antagonistHumans UProstate-specific antigen Not Available Humans UNuclear receptor subfamily 1 group I member 2 Not Available Humans - Absorption
The absolute bioavailability of a 20 mg oral dose is 69%
- Volume of distribution
Not Available
- Protein binding
98% (bound to plasma proteins, albumin and a 1-acid glycoprotein)
- Metabolism
Hepatic. Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite (RU 42 633); RU 42 698, which results from the loss of two methyl groups from position 11 beta; and RU 42 698, which results from terminal hydroxylation of the 17–propynyl chain.
Hover over products below to view reaction partners
- Route of elimination
Fecal: 83%; Renal: 9%.
- Half-life
18 hours
- Clearance
Not Available
- 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
Nearly all of the women who receive mifepristone will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Side effects include more heavy bleeding than a heavy menstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea.
- 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 softwareAbametapir The serum concentration of Mifepristone can be increased when it is combined with Abametapir. Abatacept The metabolism of Mifepristone can be increased when combined with Abatacept. Abciximab The risk or severity of adverse effects can be increased when Mifepristone is combined with Abciximab. Abemaciclib The serum concentration of Abemaciclib can be decreased when it is combined with Mifepristone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Mifepristone. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits the metabolism of mifepristone through the CYP3A4 pathway causing increased serum levels of mifepristone.
- Take with food. Taking mifepristone with meals has been shown to increase serum levels of mifepristone.
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.
- International/Other Brands
- Corlux (Corcept Therapeutics Incorporated) / Mefipil (Abbott) / Mifegyne (Exelgyn Laboratories) / Mifeprex (Danco Laboratories)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Korlym Tablet 300 mg/1 Oral Corcept Therapeutics Incorporated 2012-02-17 Not applicable US Mifepristone Tablet 300 mg/1 Oral Corcept Therapeutics Incorporated 2024-05-28 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mifepristone Tablet 200 mg/1 Oral PCI Pharma Services Canada, Inc. 2019-04-11 Not applicable US Mifepristone Tablet 200 mg/1 Oral GenBioPro, Inc. 2019-05-01 Not applicable US Mifepristone Tablet, film coated 300 mg/1 Oral Actavis Pharma, Inc. 2024-01-19 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image MEDABON Mifepristone (200 MG) + Misoprostol (0.2 MG) Tablet บริษัท ฟาร์มาแลนด์ (1982) จำกัด 2014-12-30 2020-10-13 Thailand Mifegymiso Mifepristone (200 mg) + Misoprostol (200 mcg) Kit; Tablet Buccal; Oral Linepharma International Limited 2017-01-10 Not applicable Canada Mifiso Mifepristone (200 mg) + Misoprostol (200 mcg) Kit; Tablet Buccal; Oral Linepharma International Limited Not applicable Not applicable Canada Mpm Pak Mifepristone (200 mg/1) + Ibuprofen (800 mg/1) + Misoprostol (200 ug/1) + Ondansetron (8 mg/1) Kit; Tablet; Tablet, orally disintegrating Oral Nucare Pharmaceuticals,inc. 2023-02-24 Not applicable US Mpm Pak Mifepristone (200 mg/1) + Ibuprofen (800 mg/1) + Misoprostol (200 ug/1) + Ondansetron (8 mg/1) Kit; Tablet; Tablet, orally disintegrating Oral Nucare Pharmaceuticals,inc. 2023-02-24 Not applicable US
Categories
- ATC Codes
- G03XB01 — Mifepristone
- G03XB — Progesterone receptor modulators
- G03X — OTHER SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
- G03 — SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- Drug Categories
- Abortifacient Agents
- Abortifacient Agents, Steroidal
- Adrenal Cortex Hormones
- Blood Glucose Lowering Agents
- BSEP/ABCB11 Substrates
- Contraceptive Agents, Female
- Contraceptive Agents, Hormonal
- Contraceptives, Oral
- Contraceptives, Oral, Synthetic
- Contraceptives, Postcoital
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Inhibitors
- Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Estranes
- Estrenes
- Fused-Ring Compounds
- Genito Urinary System and Sex Hormones
- Highest Risk QTc-Prolonging Agents
- Hormonal Contraceptives for Systemic Use
- Hormone Antagonists
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hypoglycemia-Associated Agents
- Luteolytic Agents
- Menstruation-Inducing Agents
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- Progestational Hormone Receptor Antagonists
- Progesterone Receptor Modulators
- Progestin Antagonist
- QTc Prolonging Agents
- Reproductive Control Agents
- Sex Hormones and Modulators of the Genital System
- Steroids
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oxosteroids. These are steroid derivatives carrying a C=O group attached to steroid skeleton.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Oxosteroids
- Direct Parent
- Oxosteroids
- Alternative Parents
- 3-oxosteroids / 17-hydroxysteroids / Dialkylarylamines / Aniline and substituted anilines / Cyclohexenones / Ynones / Tertiary alcohols / Cyclic alcohols and derivatives / Organopnictogen compounds / Organic oxides show 1 more
- Substituents
- 17-hydroxysteroid / 3-oxosteroid / Alcohol / Amine / Aniline or substituted anilines / Aromatic homopolycyclic compound / Benzenoid / Carbonyl group / Cyclic alcohol / Cyclic ketone show 17 more
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- 3-oxo steroid (CHEBI:50692) / Estrane and derivatives (C07652)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 320T6RNW1F
- CAS number
- 84371-65-3
- InChI Key
- VKHAHZOOUSRJNA-GCNJZUOMSA-N
- InChI
- InChI=1S/C29H35NO2/c1-5-15-29(32)16-14-26-24-12-8-20-17-22(31)11-13-23(20)27(24)25(18-28(26,29)2)19-6-9-21(10-7-19)30(3)4/h6-7,9-10,17,24-26,32H,8,11-14,16,18H2,1-4H3/t24-,25+,26-,28-,29-/m0/s1
- IUPAC Name
- (1S,3aS,3bS,10R,11aS)-10-[4-(dimethylamino)phenyl]-1-hydroxy-11a-methyl-1-(prop-1-yn-1-yl)-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,10H,11H,11aH-cyclopenta[a]phenanthren-7-one
- SMILES
- [H][C@@]12CC[C@@](O)(C#CC)[C@@]1(C)C[C@H](C1=CC=C(C=C1)N(C)C)C1=C3CCC(=O)C=C3CC[C@@]21[H]
References
- Synthesis Reference
Narendra Joshi, Anil Khile, Nitin Pradhan, "Novel polymorph form M of mifepristone and process for its preparation." U.S. Patent US20070105828, issued May 10, 2007.
US20070105828- General References
- Fiala C, Gemzel-Danielsson K: Review of medical abortion using mifepristone in combination with a prostaglandin analogue. Contraception. 2006 Jul;74(1):66-86. Epub 2006 May 19. [Article]
- Heikinheimo O, Kekkonen R, Lahteenmaki P: The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action. Contraception. 2003 Dec;68(6):421-6. [Article]
- Chabbert-Buffet N, Meduri G, Bouchard P, Spitz IM: Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update. 2005 May-Jun;11(3):293-307. Epub 2005 Mar 24. [Article]
- Spitz IM, Bardin CW, Benton L, Robbins A: Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med. 1998 Apr 30;338(18):1241-7. [Article]
- Piaggio G, von Hertzen H, Heng Z, Bilian X, Cheng L: Meta-analyses of randomized trials comparing different doses of mifepristone in emergency contraception. Contraception. 2003 Dec;68(6):447-52. [Article]
- Fjerstad M, Trussell J, Sivin I, Lichtenberg ES, Cullins V: Rates of serious infection after changes in regimens for medical abortion. N Engl J Med. 2009 Jul 9;361(2):145-51. doi: 10.1056/NEJMoa0809146. [Article]
- External Links
- Human Metabolome Database
- HMDB0014972
- KEGG Drug
- D00585
- KEGG Compound
- C07652
- PubChem Compound
- 55245
- PubChem Substance
- 46505795
- ChemSpider
- 49889
- BindingDB
- 18627
- 6964
- ChEBI
- 50692
- ChEMBL
- CHEMBL1276308
- ZINC
- ZINC000003831128
- Therapeutic Targets Database
- DAP000090
- PharmGKB
- PA450500
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- 486
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Mifepristone
- PDB Entries
- 1nhz / 2w8y / 3h52 / 3qt0 / 4ltw / 5uc1 / 5uc3
- FDA label
- Download (46.5 KB)
- MSDS
- Download (57.1 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 Abortion, Complete 1 somestatus stop reason just information to hide Not Available Completed Not Available Post Traumatic Stress Disorder (PTSD) 1 somestatus stop reason just information to hide Not Available Completed Health Services Research Abortion in First Trimester 2 somestatus stop reason just information to hide Not Available Completed Health Services Research Medically induced abortion 1 somestatus stop reason just information to hide Not Available Completed Health Services Research Termination of Pregnancy (TOP) 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Danco laboratories llc
- Packagers
- Danco Labs LLC
- Dosage Forms
Form Route Strength Tablet Oral 300 mg/1 Tablet Kit; tablet Buccal; Oral Tablet Oral 600 MG Tablet Oral 200 mg Tablet Oral Tablet Oral 200 mg/1 Tablet, film coated Oral 300 mg/1 Kit; tablet; tablet, orally disintegrating Oral Tablet Oral 200.00 mg Tablet Oral 200.000 mg - Prices
Unit description Cost Unit Mifeprex 200 mg tablet 90.0USD 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 US8921348 No 2014-12-30 2028-08-27 US US9829495 No 2017-11-28 2036-08-15 US US9943526 No 2018-04-17 2036-04-20 US US10006924 No 2018-06-26 2036-08-12 US US10166243 No 2019-01-01 2036-04-20 US US10166242 No 2019-01-01 2036-04-20 US US10151763 No 2018-12-11 2037-01-18 US US10195214 No 2019-02-05 2037-06-19 US US10231983 No 2019-03-19 2038-08-22 US US10314850 No 2019-06-11 2038-08-22 US US10500216 No 2019-12-10 2033-03-05 US US10495650 No 2019-12-03 2036-08-12 US US10660904 No 2020-05-26 2036-04-20 US US10780097 No 2020-09-22 2038-08-22 US US10842800 No 2020-11-24 2037-06-19 US US10842801 No 2020-11-24 2032-11-15 US US11969435 No 2017-06-19 2037-06-19 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 191-196 °C FDA Label water solubility Poorly soluble FDA Label logP 4.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00336 mg/mL ALOGPS logP 5.33 ALOGPS logP 5.13 Chemaxon logS -5.1 ALOGPS pKa (Strongest Acidic) 12.87 Chemaxon pKa (Strongest Basic) 4.89 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 40.54 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 132.58 m3·mol-1 Chemaxon Polarizability 50.69 Å3 Chemaxon Number of Rings 5 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 + 1.0 Blood Brain Barrier + 0.7135 Caco-2 permeable + 0.6716 P-glycoprotein substrate Substrate 0.643 P-glycoprotein inhibitor I Inhibitor 0.8564 P-glycoprotein inhibitor II Inhibitor 0.8387 Renal organic cation transporter Non-inhibitor 0.8177 CYP450 2C9 substrate Non-substrate 0.7606 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.8334 CYP450 1A2 substrate Inhibitor 0.9106 CYP450 2C9 inhibitor Non-inhibitor 0.6293 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Inhibitor 0.796 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6129 Ames test Non AMES toxic 0.856 Carcinogenicity Non-carcinogens 0.825 Biodegradation Not ready biodegradable 0.9971 Rat acute toxicity 2.7705 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9177 hERG inhibition (predictor II) Non-inhibitor 0.6879
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 228.3900568 predictedDarkChem Lite v0.1.0 [M-H]- 216.6296007 predictedDarkChem Lite v0.1.0 [M-H]- 226.0790568 predictedDarkChem Lite v0.1.0 [M-H]- 201.22139 predictedDeepCCS 1.0 (2019) [M+H]+ 228.0370568 predictedDarkChem Lite v0.1.0 [M+H]+ 218.2452362 predictedDarkChem Lite v0.1.0 [M+H]+ 226.6089568 predictedDarkChem Lite v0.1.0 [M+H]+ 203.61696 predictedDeepCCS 1.0 (2019) [M+Na]+ 228.3637568 predictedDarkChem Lite v0.1.0 [M+Na]+ 229.2100829 predictedDarkChem Lite v0.1.0 [M+Na]+ 226.2535568 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.5295 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as a transcriptional activator or repressor
- Specific Function
- ATPase binding
- Gene Name
- PGR
- Uniprot ID
- P06401
- Uniprot Name
- Progesterone receptor
- Molecular Weight
- 98979.96 Da
References
- Greb RR, Kiesel L, Selbmann AK, Wehrmann M, Hodgen GD, Goodman AL, Wallwiener D: Disparate actions of mifepristone (RU 486) on glands and stroma in the primate endometrium. Hum Reprod. 1999 Jan;14(1):198-206. [Article]
- Sun M, Zhu G, Zhou L: [Effect of mifepristone on the expression of progesterone receptor messenger RNA and protein in uterine leiomyomata]. Zhonghua Fu Chan Ke Za Zhi. 1998 Apr;33(4):227-31. [Article]
- Hazra BG, Basu S, Pore VS, Joshi PL, Pal D, Chakrabarti P: Synthesis of 11beta-(4-dimethylaminophenyl)-17beta-hydroxy-17alpha- (3-methyl-1-butynyl)-4, 9-estradien-3-one and 11beta-(4-acetophenyl)- 17beta-hydroxy-17alpha-(3-methyl-1-butynyl)-4, 9-estradien-3-one: two new analogs of mifepristone (RU-486). Steroids. 2000 Mar;65(3):157-62. [Article]
- Gao Y, Cheng L, Liu Y: [Failure of mifepristone induced interruption of pregnancy: point mutation at genetic codon 722 in human progesterone receptor gene]. Zhonghua Fu Chan Ke Za Zhi. 1998 Sep;33(9):549-52. [Article]
- Jiang J, Wu R, Wang Z: [Effects of mifepristone on expression of estrogen receptor and progesterone receptor in cultured human eutopic and ectopic endometria]. Zhonghua Fu Chan Ke Za Zhi. 2001 Apr;36(4):218-21. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity)
- Specific Function
- core promoter sequence-specific DNA binding
- Gene Name
- NR3C1
- Uniprot ID
- P04150
- Uniprot Name
- Glucocorticoid receptor
- Molecular Weight
- 85658.57 Da
References
- LeVan TD, Babin EA, Yamamura HI, Bloom JW: Pharmacological characterization of glucocorticoid receptors in primary human bronchial epithelial cells. Biochem Pharmacol. 1999 May 1;57(9):1003-9. [Article]
- Attardi BJ, Burgenson J, Hild SA, Reel JR: In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone. J Steroid Biochem Mol Biol. 2004 Mar;88(3):277-88. [Article]
- Aida K, Shi Q, Wang J, VandeBerg JL, McDonald T, Nathanielsz P, Wang XL: The effects of betamethasone (BM) on endothelial nitric oxide synthase (eNOS) expression in adult baboon femoral arterial endothelial cells. J Steroid Biochem Mol Biol. 2004 Aug;91(4-5):219-24. [Article]
- Gu G, Hentunen TA, Nars M, Harkonen PL, Vaananen HK: Estrogen protects primary osteocytes against glucocorticoid-induced apoptosis. Apoptosis. 2005 May;10(3):583-95. [Article]
- de Pablos RM, Villaran RF, Arguelles S, Herrera AJ, Venero JL, Ayala A, Cano J, Machado A: Stress increases vulnerability to inflammation in the rat prefrontal cortex. J Neurosci. 2006 May 24;26(21):5709-19. [Article]
- Ayalasomayajula SP, Ashton P, Kompella UB: Fluocinolone inhibits VEGF expression via glucocorticoid receptor in human retinal pigment epithelial (ARPE-19) cells and TNF-alpha-induced angiogenesis in chick chorioallantoic membrane (CAM). J Ocul Pharmacol Ther. 2009 Apr;25(2):97-103. doi: 10.1089/jop.2008.0090. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum
- Specific Function
- endopeptidase activity
- Gene Name
- KLK3
- Uniprot ID
- P07288
- Uniprot Name
- Prostate-specific antigen
- Molecular Weight
- 28741.1 Da
References
- Kang Z, Janne OA, Palvimo JJ: Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor. Mol Endocrinol. 2004 Nov;18(11):2633-48. Epub 2004 Aug 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes
- Specific Function
- DNA-binding transcription activator activity, RNA polymerase II-specific
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, 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) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- He K, Woolf TF, Hollenberg PF: Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486). J Pharmacol Exp Ther. 1999 Feb;288(2):791-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Mifepristone FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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
- PDR [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- 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
- Yueh MF, Kawahara M, Raucy J: High volume bioassays to assess CYP3A4-mediated drug interactions: induction and inhibition in a single cell line. Drug Metab Dispos. 2005 Jan;33(1):38-48. Epub 2004 Oct 1. [Article]
- Jang GR, Benet LZ: Antiprogestin pharmacodynamics, pharmacokinetics, and metabolism: implications for their long-term use. J Pharmacokinet Biopharm. 1997 Dec;25(6):647-72. [Article]
- Jang GR, Benet LZ: Antiprogestin-mediated inactivation of cytochrome P450 3A4. Pharmacology. 1998 Mar;56(3):150-7. doi: 10.1159/000028193. [Article]
- Ma B, Polsky-Fisher SL, Vickers S, Cui D, Rodrigues AD: Cytochrome P450 3A-dependent metabolism of a potent and selective gamma-aminobutyric acid Aalpha2/3 receptor agonist in vitro: involvement of cytochrome P450 3A5 displaying biphasic kinetics. Drug Metab Dispos. 2007 Aug;35(8):1301-7. doi: 10.1124/dmd.107.014753. Epub 2007 Apr 25. [Article]
- Reinen J, Smit M, Wenker M: Evaluation of Strategies for the Assessment of Drug-Drug Interactions Involving Cytochrome P450 Enzymes. Eur J Drug Metab Pharmacokinet. 2018 Dec;43(6):737-750. doi: 10.1007/s13318-018-0485-7. [Article]
- Flockhart Table of Drug Interactions [Link]
- Mifeprex (Mifepristone) FDA Label [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). 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:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion 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 all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Soars MG, Grime K, Riley RJ: Comparative analysis of substrate and inhibitor interactions with CYP3A4 and CYP3A5. Xenobiotica. 2006 Apr;36(4):287-99. doi: 10.1080/00498250500446208 . [Article]
- Khan KK, He YQ, Correia MA, Halpert JR: Differential oxidation of mifepristone by cytochromes P450 3A4 and 3A5: selective inactivation of P450 3A4. Drug Metab Dispos. 2002 Sep;30(9):985-90. [Article]
- Flockhart Table of Drug Interactions [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- 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
- Geick A, Eichelbaum M, Burk O: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem. 2001 May 4;276(18):14581-7. Epub 2001 Jan 31. [Article]
- Lecureur V, Fardel O, Guillouzo A: The antiprogestatin drug RU 486 potentiates doxorubicin cytotoxicity in multidrug resistant cells through inhibition of P-glycoprotein function. FEBS Lett. 1994 Nov 28;355(2):187-91. [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
- Payen L, Delugin L, Courtois A, Trinquart Y, Guillouzo A, Fardel O: Reversal of MRP-mediated multidrug resistance in human lung cancer cells by the antiprogestatin drug RU486. Biochem Biophys Res Commun. 1999 May 19;258(3):513-8. [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
- No
- 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
- Gui C, Miao Y, Thompson L, Wahlgren B, Mock M, Stieger B, Hagenbuch B: Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65. doi: 10.1016/j.ejphar.2008.01.042. Epub 2008 Feb 8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate 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). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). 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 pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (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)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- Gui C, Miao Y, Thompson L, Wahlgren B, Mock M, Stieger B, Hagenbuch B: Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65. doi: 10.1016/j.ejphar.2008.01.042. Epub 2008 Feb 8. [Article]
Drug created at June 13, 2005 13:24 / Updated at June 02, 2024 21:45