Diethylstilbestrol
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Diethylstilbestrol
- DrugBank Accession Number
- DB00255
- Background
A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)
The FDA withdrew its approval for the use of all oral and parenteral drug products containing 25 milligrams or more of diethylstilbestrol per unit dose.6
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
- Weight
- Average: 268.356
Monoisotopic: 268.146329884 - Chemical Formula
- C18H20O2
- Synonyms
- (E)-3,4-bis(4-hydroxyphenyl)-3-hexene
- (E)-4,4'-(1,2-diethyl-1,2-ethenediyl)bisphenol
- 4,4'-dihydroxy-α,β-diethylstilbene
- DES
- Diethylstilbestrol
- Diéthylstilbestrol
- Diethylstilbestrolum
- Dietilestilbestrol
- Stilboestrol
- trans-4,4'-(1,2-diethyl-1,2-ethenediyl)bisphenol
- trans-Diethylstilbesterol
- trans-Diethylstilbestrol
- trans-Diethylstilboesterol
- α,α'-diethyl-(E)-4,4'-stilbenediol
- External IDs
- RCRA waste number U089
Pharmacology
- Indication
Used in the treatment of prostate cancer. Previously used in the prevention of miscarriage or premature delivery in pregnant women prone to miscarriage or premature delivery.
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- Pharmacodynamics
Diethylstilbestrol is a synthetic estrogen that was developed to supplement a woman's natural estrogen production. In 1971, the Food and Drug Administration (FDA) issued a Drug Bulletin advising physicians to stop prescribing DES to pregnant women because it was linked to a rare vaginal cancer in female offspring.
- Mechanism of action
Estrogens diffuse into their target cells and interact with a protein receptor, the estrogen receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. The effect of Estrogen binding their receptors causes downstream increases the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
Target Actions Organism AEstrogen receptor beta agonistHumans AEstrogen receptor agonistHumans AEstrogen-related receptor gamma agonistHumans USteroid hormone receptor ERR1 Not Available Humans USteroid hormone receptor ERR2 Not Available Humans UNuclear receptor coactivator 2 Not Available Humans UNuclear receptor subfamily 1 group I member 2 Not Available Humans UAndrogen receptor antagonistHumans USex hormone-binding globulin Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic.
- Route of elimination
Not Available
- Half-life
Not Available
- 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
Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.
- 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 Diethylstilbestrol can be increased when it is combined with Abametapir. Abatacept The metabolism of Diethylstilbestrol can be increased when combined with Abatacept. Abciximab Diethylstilbestrol may decrease the anticoagulant activities of Abciximab. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Diethylstilbestrol. Abiraterone The metabolism of Diethylstilbestrol can be decreased when combined with Abiraterone. - Food Interactions
- Not Available
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 Diethylstilbestrol diphosphate A0E0NMA80F 522-40-7 NLORYLAYLIXTID-ISLYRVAYSA-N Diethylstilbestrol diphosphate sodium Not Available Not Available Not applicable - International/Other Brands
- Distilbene (Gerda) / Stilbestrol (Nysco) / Stilbetin (Bristol Myers-Squibb)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Honvol Ampoules 250mg Liquid 250 mg / 5 mL Intravenous Carter Horner Corp. 1956-12-31 2000-11-17 Canada Honvol Tablets 100mg Tablet 100 mg / tab Oral Carter Horner Corp. 1958-12-31 2001-05-22 Canada Stilbestrol 0.5mg Tablet Tablet .5 mg / tab Oral Glaxo Canada Inc 1993-12-31 1998-07-30 Canada Stilbestrol 1.0mg Tablet Tablet 1 mg / tab Oral Glaxo Canada Inc 1991-12-31 1996-09-10 Canada Stilbestrol Tab 1mg Tablet 1 mg / tab Oral Everest Pharmaceuticals Ltd. 1980-12-31 1999-07-14 Canada
Categories
- ATC Codes
- L02AA04 — Fosfestrol
- L02AA — Estrogens
- L02A — HORMONES AND RELATED AGENTS
- L02 — ENDOCRINE THERAPY
- L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
- L02AA — Estrogens
- L02A — HORMONES AND RELATED AGENTS
- L02 — ENDOCRINE THERAPY
- L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
- G03CC — Estrogens, combinations with other drugs
- G03C — ESTROGENS
- G03 — SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- Drug Categories
- Adrenal Cortex Hormones
- Antineoplastic Agents, Hormonal
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- Benzene Derivatives
- Benzylidene Compounds
- BSEP/ABCB11 Substrates
- Carcinogens
- COMT Substrates
- Contraceptive Agents, Female
- Contraceptive Agents, Male
- Contraceptives, Postcoital
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (strong)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Endocrine Therapy
- Estrogen Contraceptives
- Estrogens
- Estrogens, Non-Steroidal
- Genito Urinary System and Sex Hormones
- Hormonal Contraceptives for Systemic Use
- Hormones
- Hormones and Related Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Noxae
- OATP1B1/SLCO1B1 Inhibitors
- OATP2B1/SLCO2B1 substrates
- P-glycoprotein substrates
- Sex Hormones and Modulators of the Genital System
- Stilbenes
- Stilbestrols
- Synthetic Estrogens, Plain
- Thyroxine-binding globulin inducers
- Toxic Actions
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 731DCA35BT
- CAS number
- 56-53-1
- InChI Key
- RGLYKWWBQGJZGM-ISLYRVAYSA-N
- InChI
- InChI=1S/C18H20O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h5-12,19-20H,3-4H2,1-2H3/b18-17+
- IUPAC Name
- 4-[(3E)-4-(4-hydroxyphenyl)hex-3-en-3-yl]phenol
- SMILES
- CC\C(=C(\CC)C1=CC=C(O)C=C1)C1=CC=C(O)C=C1
References
- Synthesis Reference
Adler, E.,Gie, G.J. and von Euler, H.; US. Patent 2,421,401; June 3, 1947; assigned to Hoffmann-La Roche, Inc.
- General References
- Authors unspecified: Leuprolide versus diethylstilbestrol for metastatic prostate cancer. The Leuprolide Study Group. N Engl J Med. 1984 Nov 15;311(20):1281-6. [Article]
- DIECKMANN WJ, DAVIS ME, RYNKIEWICZ LM, POTTINGER RE: Does the administration of diethylstilbestrol during pregnancy have therapeutic value? Am J Obstet Gynecol. 1953 Nov;66(5):1062-81. [Article]
- Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S: Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med. 1981 Jan 1;304(1):16-21. [Article]
- Kuchera LK: Postcoital contraception with diethylstilbestrol. JAMA. 1971 Oct 25;218(4):562-3. [Article]
- Herbst AL, Ulfelder H, Poskanzer DC: Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971 Apr 15;284(15):878-81. [Article]
- Code of Federal Regulations 216.24: Drug products withdrawn or removed from the market for reasons of safety or effectiveness. [Link]
- External Links
- Human Metabolome Database
- HMDB0302859
- KEGG Drug
- D00577
- KEGG Compound
- C07620
- PubChem Compound
- 3054
- PubChem Substance
- 46507453
- ChemSpider
- 395306
- BindingDB
- 20625
- 3390
- ChEBI
- 41922
- ChEMBL
- CHEMBL411
- ZINC
- ZINC000000001290
- Therapeutic Targets Database
- DAP001011
- PharmGKB
- PA449307
- PDBe Ligand
- DES
- Wikipedia
- Diethylstilbestrol
- PDB Entries
- 1s9p / 1tt6 / 1tz8 / 4zn7
- MSDS
- Download (73.1 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 data3 Completed Treatment Prostate Cancer 1 somestatus stop reason just information to hide 2 Completed Treatment Prostate Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Bristol myers squibb
- Eli lilly and co
- Tablicaps inc
- Bayer pharmaceuticals corp
- Packagers
- Medisca Inc.
- Dosage Forms
Form Route Strength Liquid Intravenous 250 mg / 5 mL Tablet Oral 100 mg / tab Tablet Oral 1 mg / tab Tablet Oral 0.105 mg Tablet Oral 0.51 mg Tablet Oral 1.0 mg Tablet Oral .1 mg / tab Tablet Oral .5 mg / tab - Prices
Unit description Cost Unit Diethylstilbestrol powder 13.77USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 172 Adler, E.,Gie, G.J. and von Euler, H.; US. Patent 2,421,401; June 3, 1947; assigned to Hoffmann-La Roche, Inc. water solubility 12 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 5.07 HANSCH,C ET AL. (1995) logS -4.35 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 0.0109 mg/mL ALOGPS logP 4.62 ALOGPS logP 5.19 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 8.63 Chemaxon pKa (Strongest Basic) -6.5 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 40.46 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 83.24 m3·mol-1 Chemaxon Polarizability 30.69 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9973 Blood Brain Barrier - 0.5559 Caco-2 permeable + 0.8264 P-glycoprotein substrate Substrate 0.5737 P-glycoprotein inhibitor I Non-inhibitor 0.6542 P-glycoprotein inhibitor II Non-inhibitor 0.8478 Renal organic cation transporter Non-inhibitor 0.8465 CYP450 2C9 substrate Non-substrate 0.8149 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.5107 CYP450 1A2 substrate Inhibitor 0.9106 CYP450 2C9 inhibitor Inhibitor 0.9064 CYP450 2D6 inhibitor Non-inhibitor 0.7017 CYP450 2C19 inhibitor Inhibitor 0.9198 CYP450 3A4 inhibitor Inhibitor 0.8361 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9488 Ames test Non AMES toxic 0.9579 Carcinogenicity Non-carcinogens 0.6772 Biodegradation Not ready biodegradable 0.9111 Rat acute toxicity 1.9462 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6894 hERG inhibition (predictor II) Non-inhibitor 0.6408
Spectra
- Mass Spec (NIST)
- Download (9.87 KB)
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0900000000-c4fbb2f3c4ae36dbd549 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00kr-0590000000-8f7d0588929e8670ba31 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0079-0090000000-a53859d9ad1018296832 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0ap0-0910000000-c5ed1ff5fbab2606b396 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-02ta-0960000000-7fb474a4c4d3f75c040b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0ap0-0920000000-eb521fa94e56d06dc377 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]- 180.1104226 predictedDarkChem Lite v0.1.0 [M-H]- 176.7447226 predictedDarkChem Lite v0.1.0 [M-H]- 172.23872 predictedDeepCCS 1.0 (2019) [M+H]+ 181.2490226 predictedDarkChem Lite v0.1.0 [M+H]+ 177.0546226 predictedDarkChem Lite v0.1.0 [M+H]+ 174.59673 predictedDeepCCS 1.0 (2019) [M+Na]+ 181.2706226 predictedDarkChem Lite v0.1.0 [M+Na]+ 175.5832226 predictedDarkChem Lite v0.1.0 [M+Na]+ 180.69165 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560)
- Specific Function
- DNA binding
- Gene Name
- ESR2
- Uniprot ID
- Q92731
- Uniprot Name
- Estrogen receptor beta
- Molecular Weight
- 59215.765 Da
References
- Authors unspecified: Final amended report on the safety assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in cosmetic products. Int J Toxicol. 2008;27 Suppl 4:1-82. doi: 10.1080/10915810802548359. [Article]
- Geistlinger TR, McReynolds AC, Guy RK: Ligand-selective inhibition of the interaction of steroid receptor coactivators and estrogen receptor isoforms. Chem Biol. 2004 Feb;11(2):273-81. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity)
- Specific Function
- 14-3-3 protein binding
- Gene Name
- ESR1
- Uniprot ID
- P03372
- Uniprot Name
- Estrogen receptor
- Molecular Weight
- 66215.45 Da
References
- Munoz G, Ovilo C, Estelle J, Silio L, Fernandez A, Rodriguez C: Association with litter size of new polymorphisms on ESR1 and ESR2 genes in a Chinese-European pig line. Genet Sel Evol. 2007 Mar-Apr;39(2):195-206. Epub 2007 Feb 17. [Article]
- Dixon A, Wells CC, Singh S, Babayan R, Maric C: Renoprotective effects of a selective estrogen receptor modulator, raloxifene, in an animal model of diabetic nephropathy. Am J Nephrol. 2007;27(2):120-8. Epub 2007 Feb 15. [Article]
- Hart SA, Snyder MA, Smejkalova T, Woolley CS: Estrogen mobilizes a subset of estrogen receptor-alpha-immunoreactive vesicles in inhibitory presynaptic boutons in hippocampal CA1. J Neurosci. 2007 Feb 21;27(8):2102-11. [Article]
- Baron S, Escande A, Alberola G, Bystricky K, Balaguer P, Richard-Foy H: Estrogen receptor alpha and the activating protein-1 complex cooperate during insulin-like growth factor-I-induced transcriptional activation of the pS2/TFF1 gene. J Biol Chem. 2007 Apr 20;282(16):11732-41. Epub 2007 Feb 22. [Article]
- Bains M, Cousins JC, Roberts JL: Neuroprotection by estrogen against MPP+-induced dopamine neuron death is mediated by ERalpha in primary cultures of mouse mesencephalon. Exp Neurol. 2007 Apr;204(2):767-76. Epub 2007 Jan 25. [Article]
- Kwok KC, Cheung NH: Measuring binding kinetics of ligands with tethered receptors by fluorescence polarization and total internal reflection fluorescence. Anal Chem. 2010 May 1;82(9):3819-25. doi: 10.1021/ac1002245. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Orphan receptor that acts as a transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle
- Specific Function
- AF-2 domain binding
- Gene Name
- ESRRG
- Uniprot ID
- P62508
- Uniprot Name
- Estrogen-related receptor gamma
- Molecular Weight
- 51305.485 Da
References
- Greschik H, Flaig R, Renaud JP, Moras D: Structural basis for the deactivation of the estrogen-related receptor gamma by diethylstilbestrol or 4-hydroxytamoxifen and determinants of selectivity. J Biol Chem. 2004 Aug 6;279(32):33639-46. Epub 2004 May 24. [Article]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Tremblay GB, Kunath T, Bergeron D, Lapointe L, Champigny C, Bader JA, Rossant J, Giguere V: Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR beta. Genes Dev. 2001 Apr 1;15(7):833-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle
- Specific Function
- DNA-binding transcription factor activity
- Gene Name
- ESRRA
- Uniprot ID
- P11474
- Uniprot Name
- Steroid hormone receptor ERR1
- Molecular Weight
- 45509.11 Da
References
- Tremblay GB, Kunath T, Bergeron D, Lapointe L, Champigny C, Bader JA, Rossant J, Giguere V: Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR beta. Genes Dev. 2001 Apr 1;15(7):833-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity (PubMed:17920186, PubMed:19755138). Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells. Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:23836911). Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (PubMed:17920186, PubMed:19755138). During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation. This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity)
- Specific Function
- cis-regulatory region sequence-specific DNA binding
- Gene Name
- ESRRB
- Uniprot ID
- O95718
- Uniprot Name
- Steroid hormone receptor ERR2
- Molecular Weight
- 48053.14 Da
References
- Tremblay GB, Kunath T, Bergeron D, Lapointe L, Champigny C, Bader JA, Rossant J, Giguere V: Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR beta. Genes Dev. 2001 Apr 1;15(7):833-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:23508108, PubMed:8670870, PubMed:9430642). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:23508108, PubMed:8670870, PubMed:9430642). Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression (PubMed:23508108, PubMed:8670870, PubMed:9430642). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:23508108). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (By similarity)
- Specific Function
- aryl hydrocarbon receptor binding
- Gene Name
- NCOA2
- Uniprot ID
- Q15596
- Uniprot Name
- Nuclear receptor coactivator 2
- Molecular Weight
- 159155.645 Da
References
- Geistlinger TR, McReynolds AC, Guy RK: Ligand-selective inhibition of the interaction of steroid receptor coactivators and estrogen receptor isoforms. Chem Biol. 2004 Feb;11(2):273-81. [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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3
- Specific Function
- androgen binding
- Gene Name
- AR
- Uniprot ID
- P10275
- Uniprot Name
- Androgen receptor
- Molecular Weight
- 99187.115 Da
References
- Tamura H, Ishimoto Y, Fujikawa T, Aoyama H, Yoshikawa H, Akamatsu M: Structural basis for androgen receptor agonists and antagonists: interaction of SPEED 98-listed chemicals and related compounds with the androgen receptor based on an in vitro reporter gene assay and 3D-QSAR. Bioorg Med Chem. 2006 Nov 1;14(21):7160-74. Epub 2006 Jul 28. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration
- Specific Function
- androgen binding
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
References
- Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. [Article]
- Kuzbari O, Peterson CM, Franklin MR, Hathaway LB, Johnstone EB, Hammoud AO, Lamb JG: Comparative analysis of human CYP3A4 and rat CYP3A1 induction and relevant gene expression by bisphenol A and diethylstilbestrol: implications for toxicity testing paradigms. Reprod Toxicol. 2013 Jun;37:24-30. doi: 10.1016/j.reprotox.2013.01.005. Epub 2013 Feb 4. [Article]
- 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
References
- Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. [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 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
- Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. [Article]
- Renwick AB, Surry D, Price RJ, Lake BG, Evans DC: Metabolism of 7-benzyloxy-4-trifluoromethyl-coumarin by human hepatic cytochrome P450 isoforms. Xenobiotica. 2000 Oct;30(10):955-69. doi: 10.1080/00498250050200113 . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol
- Specific Function
- catechol O-methyltransferase activity
- Gene Name
- COMT
- Uniprot ID
- P21964
- Uniprot Name
- Catechol O-methyltransferase
- Molecular Weight
- 30036.77 Da
References
- Engel LL, Weidenfield J, Merriam GR: Metabolism of diethylstilbestrol by rat liver: a preliminary report. J Toxicol Environ Health Suppl. 1976;1:37-44. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (PubMed:27702664, PubMed:2848247). Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid (PubMed:20385561). Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen (PubMed:22773874). Also displays 2-hydroxylase activity toward estrone (PubMed:22773874). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:20385561, PubMed:22773874)
- Specific Function
- aromatase activity
- Gene Name
- CYP19A1
- Uniprot ID
- P11511
- Uniprot Name
- Aromatase
- Molecular Weight
- 57882.48 Da
References
- Imamichi Y, Sekiguchi T, Kitano T, Kajitani T, Okada R, Inaoka Y, Miyamoto K, Uwada J, Takahashi S, Nemoto T, Mano A, Khan MRI, Islam MT, Yuhki KI, Kashiwagi H, Ushikubi F, Suzuki N, Taniguchi T, Yazawa T: Diethylstilbestrol administration inhibits theca cell androgen and granulosa cell estrogen production in immature rat ovary. Sci Rep. 2017 Aug 21;7(1):8374. doi: 10.1038/s41598-017-08780-7. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain
- Specific Function
- hormone activity
- Gene Name
- TTR
- Uniprot ID
- P02766
- Uniprot Name
- Transthyretin
- Molecular Weight
- 15886.88 Da
Transporters
- 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
References
- Sugimoto Y, Tsukahara S, Imai Y, Sugimoto Y, Ueda K, Tsuruo T: Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther. 2003 Jan;2(1):105-12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Rao US, Fine RL, Scarborough GA: Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
- Karlgren M, Ahlin G, Bergstrom CA, Svensson R, Palm J, Artursson P: In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions. Pharm Res. 2012 Feb;29(2):411-26. doi: 10.1007/s11095-011-0564-9. Epub 2011 Aug 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity 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:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76697.93 Da
References
- Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [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]
Drug created at June 13, 2005 13:24 / Updated at October 03, 2024 07:20