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Identification
- Summary
Elagolix is a gonadotropin releasing hormone receptor antagonist used to treat moderate to severe pain in endometriosis.
- Brand Names
- Oriahnn 28 Day Kit, Orilissa
- Generic Name
- Elagolix
- DrugBank Accession Number
- DB11979
- Background
Elagolix has been used in trials studying the basic science and treatment of Endometriosis, Folliculogenesis, Uterine Fibroids, Heavy Uterine Bleeding, and Heavy Menstrual Bleeding. As of 24 July 2018, however, the U.S. Food and Drug Administration (FDA) approved AbbVie's elagolix under the brand name Orilissa as the first and only oral gonadotropin-releasing hormone (GnRH) antagonist specifically developed for women with moderate to severe endometriosis pain 7.
It has been determined that endometriosis is one of the most common gynecologic disorders in the United States 4,5,6. In particular, estimates suggest that one in ten women of reproductive age is affected by endometriosis and experience debilitating pain symptoms 4,5,6. Moreover, women who are affected by this condition can suffer for up to six to ten years and visit multiple physicians before receiving a proper diagnosis 4,5,6. Subsequently, as Orilissa (elagolix) was approved by the FDA under priority review 7, this expedited new approval gives healthcare professionals another valuable option for treating the potentially unmet needs of women who are affected by endometriosis, depending on their specific type and severity of endometriosis pain.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Elagolix (DB11979)
- Weight
- Average: 631.6
Monoisotopic: 631.210561893 - Chemical Formula
- C32H30F5N3O5
- Synonyms
- Elagolix
- External IDs
- ABT-620
- NBI 56418
- NBI-56418
Pharmacology
- Indication
Elagolix is a gonadotropin-releasing hormone (GnRH) receptor antagonist indicated for the management of moderate to severe pain associated with endometriosis Label.
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 Used in combination to treat Heavy menstrual bleeding Combination Product in combination with: Norethisterone (DB00717), Estradiol (DB00783) •••••••••••• ••••••••••••• ••••••• Management of Moderate to severe pain •••••••••••• •••••• - Contraindications & Blackbox Warnings
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During a three menstrual cycle study in healthy women, an elagolix 150 mg once daily regimen and a 200 mg twice daily regimen resulted in an ovulation rate of about 50% and 32%, respectively Label. In Phase 3 trials in women with endometriosis, elagolix caused a dose-dependent reduction in median estradiol concentrations to approximately 42 pg/mL for the 150 mg once daily regimen and 12 pg/mL for the 200 mg twice daily regimen Label.
Furthermore, the effect of elagolix on the QTc interval was investigated in a randomized, placebo- and positive-controlled, open-label, single-dose, crossover thorough QTc study in 48 healthy adult premenopausal women Label. Elagolix concentrations in subjects administered a single dose of 1200 mg was seventeen times higher than the concentration in subjects given elagolix 200 mg twice daily. Nevertheless, there was no clinically relevant prolongation of the QTc interval Label.
- Mechanism of action
Endometriosis develops when tissue that is similar to the kind that is normally located in the uterus starts to grow outside of the uterus 4,6. Such growth leads to various symptoms like pain during periods, pelvic pain between periods, and pain during sexual intercourse 4,6. The growths themselves are referred to as lesions and frequently develop on the ovaries, fallopian tubes, and other areas around the uterus, including the bowel or bladder 4,6. The growth of these lesions is dependent upon the estrogen hormone 4.
Elagolix is an orally-administered, nonpeptide small molecule gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland Label,1,2,3. Administration of elagolix results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone.
Target Actions Organism AGonadotropin-releasing hormone receptor antagonistHumans - Absorption
The Tmax of elagolix is reported as being 1.0 hours Label. The effect of a high-fat meal (relative to fasting) can result in a reduction of the AUC and Cmax by as much as 24% and 36%, respectively Label.
- Volume of distribution
The apparent volume of distribution at steady state (Vdss/F) of elagolix is reported to be 1674 for a 150 mg daily regimen and 881 for a 200 mg twice daily regimen Label.
- Protein binding
The percentage bound to human plasma proteins for elagolix has been documented as 80% Label.
- Metabolism
Elagolix is predominantly metabolized by the CYP3A family of isoenzymes despite participating in minor metabolic pathways with the CYP2D6, CYP2C8, and uridine glucuronosyl transferases (UGTs) enzymes as well Label. The primary metabolite of elagolix, referred to as NBI-61962 (R-(+)-4-{2-[5-(2-fluoro-3-hydroxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino}-butyrate) 2, is not believed to possess any significant biologic activity due to its low plasma exposure and an observed potency that is exceptionally less than the parent elagolix compound (Ki value of 3.5 compared to 0.9 nM) 1.
- Route of elimination
The primary route of elimination of elagolix is via hepatic metabolism Label.
- Half-life
The terminal phase elimination half-life of elagolix is recorded as being 4 to 6 hours Label.
- Clearance
The oral clearance (CL/F) of elagolix is 123 L/hr for a 150 mg once daily regimen and 144 L/hr for a 200 mg twice daily regimen Label.
- Adverse Effects
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In case of overdose, monitor the patient for any signs or symptoms of adverse reactions and initiate appropriate symptomatic treatment, as needed Label. Common adverse reactions of elagolix include hot flush, headache, nausea, insomnia, mood alterations, amenorrhea, depression, anxiety, arthralgia, bone loss, changes in menstrual bleeding patterns, suicidal ideation and behavior, exacerbation of existing mood disorders, and/or hepatic transaminase elevations Label.
The recommended duration of use for elagolix is up to 24 months for the 150 mg once daily dose and up to six months for the 200 mg twice daily dose, as it causes a dose-dependent decrease in bone mineral density (BMD) Label. BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment Label. For women with moderate hepatic impairment, the recommended dosage is 150 mg once daily for up to six months Label.
- 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 softwareAbatacept The metabolism of Elagolix can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Elagolix. Abiraterone The metabolism of Elagolix can be decreased when combined with Abiraterone. Abrocitinib The serum concentration of Elagolix can be increased when it is combined with Abrocitinib. Acebutolol The metabolism of Elagolix can be decreased when combined with Acebutolol. - Food Interactions
- Administer calcium supplement. This will minimize the risk of bone mineral density loss.
- Administer vitamin supplements. Administer Vitamin D supplements to minimize the risk of bone mineral density loss.
- Take at the same time every day.
- Take with or without food.
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 Elagolix sodium 5948VUI423 832720-36-2 DQYGXRQUFSRDCH-UQIIZPHYSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Orilissa Tablet 200 mg Oral Abbvie 2019-05-24 Not applicable Canada 
Orilissa Tablet, film coated 150 mg/1 Oral Abbvie 2018-07-23 Not applicable US 
Orilissa Tablet 150 mg Oral Abbvie 2018-10-30 Not applicable Canada Orilissa Tablet, film coated 200 mg/1 Oral Abbvie 2018-07-23 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Oriahnn Elagolix sodium (300 mg/1) + Elagolix sodium (300 mg/1) + Estradiol (1 mg/1) + Norethisterone (0.5 mg/1) Capsule; Kit Oral Abbvie 2020-05-29 Not applicable US Oriahnn Elagolix sodium (300 mg/1) + Elagolix sodium (300 mg/1) + Estradiol (1 mg/1) + Norethisterone (0.5 mg/1) Capsule; Kit Oral Abbvie 2020-05-29 Not applicable US
Categories
- ATC Codes
- H01CC53 — Elagolix, estradiol and norethisterone
- H01CC — Anti-gonadotropin-releasing hormones
- H01C — HYPOTHALAMIC HORMONES
- H01 — PITUITARY AND HYPOTHALAMIC HORMONES AND ANALOGUES
- H — SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS
- Drug Categories
- Anti-Gonadotropin-Releasing Hormones
- Antigonadotropins and Similar Agents
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Decreased GnRH Secretion
- Gonadotropin Releasing Hormone Receptor Antagonists
- Gonadotropin-releasing Hormone Antagonists
- Hydrocarbons, Halogenated
- Hypothalamic Hormones
- OATP1B1/SLCO1B1 Substrates
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Pituitary and Hypothalamic Hormones and Analogues
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Gamma amino acids and derivatives
- Alternative Parents
- Trifluoromethylbenzenes / Anisoles / Methoxybenzenes / Phenoxy compounds / Aralkylamines / Alkyl aryl ethers / Amino fatty acids / Fluorobenzenes / Pyrimidones / Hydropyrimidines show 16 more
- Substituents
- Alkyl aryl ether / Alkyl fluoride / Alkyl halide / Amine / Amino acid / Amino fatty acid / Anisole / Aralkylamine / Aromatic heteromonocyclic compound / Aryl fluoride show 35 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 5B2546MB5Z
- CAS number
- 834153-87-6
- InChI Key
- HEAUOKZIVMZVQL-VWLOTQADSA-N
- InChI
- InChI=1S/C32H30F5N3O5/c1-19-28(21-11-6-14-26(45-2)29(21)34)30(43)40(18-25(20-9-4-3-5-10-20)38-16-8-15-27(41)42)31(44)39(19)17-22-23(32(35,36)37)12-7-13-24(22)33/h3-7,9-14,25,38H,8,15-18H2,1-2H3,(H,41,42)/t25-/m0/s1
- IUPAC Name
- 4-{[(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-4-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-1-yl]-1-phenylethyl]amino}butanoic acid
- SMILES
- COC1=CC=CC(=C1F)C1=C(C)N(CC2=C(C=CC=C2F)C(F)(F)F)C(=O)N(C[C@H](NCCCC(O)=O)C2=CC=CC=C2)C1=O
References
- General References
- Ezzati M, Carr BR: Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain. Womens Health (Lond). 2015 Jan;11(1):19-28. doi: 10.2217/whe.14.68. [Article]
- Struthers RS, Nicholls AJ, Grundy J, Chen T, Jimenez R, Yen SS, Bozigian HP: Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix. J Clin Endocrinol Metab. 2009 Feb;94(2):545-51. doi: 10.1210/jc.2008-1695. Epub 2008 Nov 25. [Article]
- Melis GB, Neri M, Corda V, Malune ME, Piras B, Pirarba S, Guerriero S, Orru M, D'Alterio MN, Angioni S, Paoletti AM: Overview of elagolix for the treatment of endometriosis. Expert Opin Drug Metab Toxicol. 2016 May;12(5):581-8. doi: 10.1517/17425255.2016.1171316. [Article]
- Giudice LC: Clinical practice. Endometriosis. N Engl J Med. 2010 Jun 24;362(25):2389-98. doi: 10.1056/NEJMcp1000274. [Article]
- Nnoaham KE, Hummelshoj L, Webster P, d'Hooghe T, de Cicco Nardone F, de Cicco Nardone C, Jenkinson C, Kennedy SH, Zondervan KT: Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011 Aug;96(2):366-373.e8. doi: 10.1016/j.fertnstert.2011.05.090. Epub 2011 Jun 30. [Article]
- U.S. Department of Health and Human Services (2002): Endometriosis [File]
- AbbVie Orilissa (elagolix) FDA Approval Press Release [File]
- External Links
- Human Metabolome Database
- HMDB0304892
- PubChem Compound
- 11250647
- PubChem Substance
- 347828301
- ChemSpider
- 9425680
- 2049846
- ChEBI
- 177453
- ChEMBL
- CHEMBL1208155
- ZINC
- ZINC000049888891
- PDBe Ligand
- F5O
- Wikipedia
- Elagolix
- PDB Entries
- 7br3
- FDA label
- Download (631 KB)
- MSDS
- Download (174 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Fibroid Uterus / Menstrual Bleeding, Heavy 1 somestatus stop reason just information to hide 4 Completed Treatment Uterine Fibroids (Leiomyomas) 1 somestatus stop reason just information to hide 4 Recruiting Basic Science Cerebrovascular Diseases 1 somestatus stop reason just information to hide 4 Recruiting Treatment Mild Autonomous Cortisol Excess 1 somestatus stop reason just information to hide 4 Unknown Status Screening Ovulation; Failure or Lack of 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule; kit Oral Tablet Oral 150 mg Tablet Oral 200 mg Tablet, film coated Oral 150 mg/1 Tablet, film coated Oral 200 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7419983 No 2008-09-02 2024-07-06 US US7462625 No 2008-12-09 2021-01-25 US US7176211 No 2007-02-13 2024-07-06 US US7179815 No 2007-02-20 2021-03-07 US US7056927 No 2006-06-06 2024-09-10 US US6872728 No 2005-03-29 2021-01-25 US US10537572 No 2020-01-21 2036-09-01 US US10682351 No 2020-06-16 2036-09-01 US US10881659 No 2021-01-05 2034-03-14 US US11045470 No 2021-06-29 2034-03-14 US US11344551 No 2014-03-14 2034-03-14 US US11459305 No 2008-11-07 2028-11-07 US US11542239 No 2019-07-23 2039-07-23 US US11690854 No 2018-04-19 2038-04-19 US US11690845 No 2020-08-27 2040-08-27 US US11707464 No 2014-03-14 2034-03-14 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility <1 mg/mL MSDS - Predicted Properties
Property Value Source Water Solubility 0.00243 mg/mL ALOGPS logP 4.68 ALOGPS logP 3.14 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 3.86 Chemaxon pKa (Strongest Basic) 9.04 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 99.18 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 156.06 m3·mol-1 Chemaxon Polarizability 59.44 Å3 Chemaxon Number of Rings 4 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 230.15904 predictedDeepCCS 1.0 (2019) [M+H]+ 231.98392 predictedDeepCCS 1.0 (2019) [M+Na]+ 237.58974 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling
- Specific Function
- gonadotropin-releasing hormone receptor activity
- Gene Name
- GNRHR
- Uniprot ID
- P30968
- Uniprot Name
- Gonadotropin-releasing hormone receptor
- Molecular Weight
- 37730.355 Da
References
- Chen C, Wu D, Guo Z, Xie Q, Reinhart GJ, Madan A, Wen J, Chen T, Huang CQ, Chen M, Chen Y, Tucci FC, Rowbottom M, Pontillo J, Zhu YF, Wade W, Saunders J, Bozigian H, Struthers RS: Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4 -methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor. J Med Chem. 2008 Dec 11;51(23):7478-85. doi: 10.1021/jm8006454. [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 group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
Components:
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- 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
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity)
- Specific Function
- enzyme binding
Components:
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Elagolix is both a substrate and inhibitor of P-glycoprotein. The effect of concomitant use of P-glycoprotein inhibitors or inducers on the pharmacokinetics of elagolix is unknown.
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
Drug created at October 20, 2016 21:07 / Updated at August 26, 2024 19:23