Detailed Information (TTD) -- BIDD

TTD Target ID: TTDS00242

Target Information
Name	Estrogen receptor
Type of target	Successful target
Synonyms	ER
	ER-alpha
	ERalpha
	Estradiol receptor
	Estrogen receptor alpha
	Oestrogen receptor
	Oestrogen receptor alpha
Disease	Brain injury [1]
	Breast cancer [2][3][4][5]
	Cardiovascular disease, unspecified [5]
	Coronary atherosclerosis [6]
	Endocrine independent cancer [2]
	Neurodegenerative diseases [5]
	Osteoporosis, unspecified [7]
	Postmenopausal symptoms [6]
Drug(s)	Chlorotrianisene	Approved	Menopause	[8]
	Clomifene	Approved	Female infertility	[9]
	Danazol	Approved	Menorrhagia	[10]
	Dienestrol	Approved	Atrophic vaginitis	[11]
	Diethylstilbestrol	Approved	Gonorrheal vaginitis	[12]
	Estradiol	Approved	Hormone replacement therapy	[13]
	Estriol	Approved	Multiple sclerosis	[13]
	Estrone	Approved	Menopausal and postmenopausal disorders	[13]
	Ethinyl Estradiol	Approved	Female hypogonadism	[14][13]
	Fulvestrant	Approved	Breast Cancer	[15]
	Lasofoxifene	Approved	Osteoporosis	[16]
	Mestranol	Approved	First oral contraceptives	[17]
	Mitotane	Approved	Adrenocortical carcinoma	[18][19]
	Quinestrol	Approved	Breast cancer and prostate cancer	[20]
	Raloxifene	Approved	Osteoporosis in post-menopausal women	[7]
	Tamoxifen	Approved	Breast cancer	[21][22]
	Toremifene	Approved	Breast Cancer	[23]
	Ospemifene	Phase III	Post-menopausal vaginal atrophy	[24]
	Estrogen and selective estrogen receptor modulators	Preclinical	Parkinson��s Disease	[25]
BioChemical Class	Zinc-finger
UniProt ID	P03372
	Q13262
PDB Structure	1HCQ; 1L2I; 1PCG; 1QKT; 1QKU; 1R5K; 1SJ0; 1UOM.
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.
Sequence	MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAY EFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPF LQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAK ETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQAC RLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKR SKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINW AKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEG MVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLD KITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLL LEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
Related US Patent	6,340,774
	6,355,670
	6,403,611
	6,524,805
	6,613,796
Target Validation	Click to Find Target Validation Information.
QSAR Model	Click to Find Target QSAR Model.
Inhibitor	2,3-diphenyl-1H-indole	[26]
	4-Naphthalen-2-yl-phenol	[27]
	6-Phenyl-naphthalen-2-ol	[27]
	7-Phenyl-naphthalen-2-ol	[27]
	8-benzylnaringenin	[28]
	8-methylnaringenin	[28]
	8-n-heptylnaringenin	[28]
	8-n-nonylnaringenin	[28]
	8-n-pentylnaringenin	[28]
	8-n-propylnaringenin	[28]
	8-n-undecylnaringenin	[28]
	ANDROSTENEDIOL	[29]
	ARZOXIFENE	[30]
	BITHIONOL	[31]
	BROUSSONIN A	[32]
	COUMESTROL	[33]
	CP-394531	[34]
	CP-409069	[34]
	DIADZEIN	[35]
	DIHYDRORALOXIFENE	[36]
	EFFUSOL	[37]
	GSK-5182	[38]
	Genistein	[39]
	HEXESTROL	[40]
	ICI-164384	[41]
	JNJ-17148066	[42]
	JNJ-19398990	[42]
	JNJ-26529126	[42]
	JNJ-26529152	[42]
	LTERHKILHRLLQEGSPSD	[43]
	LY-117018	[44]
	MPrP	[45]
	NAFOXIDINE	[46]
	ONAPRISTONE	[47]
	Pipendoxifene	[48]
	RALOXIFENE CORE	[49]
	SOPHORAFLAVANONE B	[28]
	Tamoxifen butyl bromide	[50]
	Tamoxifen ethyl bromide	[50]
	Tamoxifen isopropyl bromide	[50]
	Tamoxifen methyl iodide	[50]
	WAY-169916	[51]
	ZK-119010	[52]
	ZK-164015	[53]
Agonist	Dienestrol	[11]
	Diethylstilbestrol	[12]
	Estradiol	[13]
	Estriol	[13]
	Estrogen	[6]
	Estrone	[13]
	Ethinyl Estradiol	[14][13]
	Mestranol	[17]
Antagonist	Danazol	[10]
	EM-800	[54]
	Fulvestrant	[15]
	GW7604	[55]
	Tamoxifen	[21][22]
	Trans-hydroxytamoxifen	[56]
Modulator	Clomifene	[9]
	Estrogen and selective estrogen receptor modulators	[25]
	Lasofoxifene	[16]
	Ospemifene	[24]
	Quinestrol	[20]
	Raloxifene	[7]
	Toremifene	[23]
Binder	Chlorotrianisene	[8]
	Mitotane	[18][19]
Cross References	3D Structure Related Literature On-Line Medical Dictionary
Ref 1	Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1952-7. Epub 2001 Feb 6. To Reference
Ref 2	Targeting oestrogen to kill the cancer but not the patient. Br J Cancer. 2004 Mar 8;90(5):944-9. To Reference
Ref 3	Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function. Br J Cancer. 2004 Feb 23;90(4):853-9. To Reference
Ref 4	How does the estrogen receptor work? Breast Cancer Res. 2002;4(2):62-4. Epub 2002 Feb 13. To Reference
Ref 5	Non-genomic steroid effects: estrogen action revisited. Ann Endocrinol (Paris). 2000 Dec;61(6):517-523. To Reference
Ref 6	Estrogen-receptor polymorphisms and effects of estrogen replacement on high-density lipoprotein cholesterol in women with coronary disease. N Engl J Med. 2002 Mar 28;346(13):967-74. To Reference
Ref 7	Raloxifene: risks and benefits. Ann N Y Acad Sci. 2001 Dec;949:295-303. To Reference
Ref 8	Inactivation of the uterine estrogen receptor binding of estradiol during P-450 catalyzed metabolism of chlorotrianisene (TACE). Speculation that TACE antiestrogenic activity involves covalent binding to the estrogen receptor. FEBS Lett. 1990 Feb 12;261(1):59-62. To Reference
Ref 9	The future of the new selective estrogen receptor modulators. Menopause Int. 2007 Mar;13(1):27-34. To Reference
Ref 10	Danazol suppression of luteinizing hormone in the rat: evidence for mediation by both androgen and estrogen receptors. Proc Soc Exp Biol Med. 1990 May;194(1):54-7. To Reference
Ref 11	Potential use of an estrogen-glucocorticoid receptor chimera as a drug screen for tissue selective estrogenic activity. Bone. 2009 Jan;44(1):102-12. Epub 2008 Oct 11. To Reference
Ref 12	Effects of Diethylstilbestrol on Programmed Oocyte Death and Induction of Polyovular Follicles in Neonatal Mouse Ovaries. Biol Reprod. 2009 Jun 24. [Epub ahead of print] To Reference
Ref 13	Reprint of Are all estrogens the same? Maturitas. 2008 Sep-Oct;61(1-2):195-201. To Reference
Ref 14	17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Jan 23. [Epub ahead of print] To Reference
Ref 15	Beta3-tubulin is induced by estradiol in human breast carcinoma cells through an estrogen-receptor dependent pathway. Cell Motil Cytoskeleton. 2009 Jul;66(7):378-88. To Reference
Ref 16	Pfizer. Product Development Pipeline. March 31 2009. To Reference
Ref 17	Short-term effects of environmentally relevant concentrations of EDC mixtures on Mytilus galloprovincialis digestive gland. Aquat Toxicol. 2008 May 30;87(4):272-9. Epub 2008 Mar 10. To Reference
Ref 18	Mitotane for adrenocortical carcinoma treatment. Curr Opin Investig Drugs. 2005 Apr;6(4):386-94. To Reference
Ref 19	Mitotane has an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans. J Clin Endocrinol Metab. 2006 Jun;91(6):2165-70. Epub 2006 Mar 21. To Reference
Ref 20	The antioxidant effect of estrogen and Selective Estrogen Receptor Modulators in the inhibition of osteocyte apoptosis in vitro. Bone. 2007 Mar;40(3):674-84. Epub 2006 Dec 13. To Reference
Ref 21	Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):165-86. To Reference
Ref 22	Chemoprevention for high-risk women: tamoxifen and beyond. Breast J. 2001 Sep-Oct;7(5):311-20. To Reference
Ref 23	Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithelial cells. Prostate Cancer Prostatic Dis. 2009 May 26. [Epub ahead of print] To Reference
Ref 24	2011 Pipeline of Shionogi. To Reference
Ref 25	Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42. To Reference
Ref 26	Bioorg Med Chem Lett. 2005 Dec 15;15(24):5562-6. Epub 2005 Oct 10.Estrogen receptor beta selective ligands: discovery and SAR of novel heterocyclic ligands. To Reference
Ref 27	J Med Chem. 2005 Jun 16;48(12):3953-79.ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERbeta selectivity. To Reference
Ref 28	J Med Chem. 2006 Dec 14;49(25):7357-65.Subtle side-chain modifications of the hop phytoestrogen 8-prenylnaringenin result in distinct agonist/antagonist activity profiles for estrogen receptors alpha and beta. To Reference
Ref 29	Bioorg Med Chem Lett. 2007 Nov 15;17(22):6295-8. Epub 2007 Sep 7.Androstene-3,5-dienes as ER-beta selective SERMs. To Reference
Ref 30	J Med Chem. 2007 May 31;50(11):2682-92. Epub 2007 May 10.Benzothiophene selective estrogen receptor modulators with modulated oxidative activity and receptor affinity. To Reference
Ref 31	Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). To Reference
Ref 32	Bioorg Med Chem Lett. 2010 Jun 15;20(12):3764-7. Epub 2010 Apr 19.New estrogenic compounds isolated from Broussonetia kazinoki. To Reference
Ref 33	J Med Chem. 2005 May 19;48(10):3463-6.Structure-based virtual screening for plant-based ERbeta-selective ligands as potential preventative therapy against age-related neurodegenerative diseases. To Reference
Ref 34	J Med Chem. 2002 Jun 6;45(12):2417-24.Discovery of potent, nonsteroidal, and highly selective glucocorticoid receptor antagonists. To Reference
Ref 35	J Nat Prod. 2002 Dec;65(12):1749-53.Isolation and structure elucidation of an isoflavone and a sesterterpenoic acid from Henriettella fascicularis. To Reference
Ref 36	Bioorg Med Chem Lett. 1999 Apr 19;9(8):1137-40.Synthesis and biological activity of trans-2,3-dihydroraloxifene. To Reference
Ref 37	Bioorg Med Chem Lett. 2006 Mar 15;16(6):1468-72. Epub 2006 Jan 18.6H-Benzo[c]chromen-6-one derivatives as selective ERbeta agonists. To Reference
Ref 38	Bioorg Med Chem Lett. 2006 Feb 15;16(4):821-4. Epub 2005 Nov 22.Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma. To Reference
Ref 39	Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 40	Bioorg. Med. Chem. Lett. 6(9):1047-1050 (1996) To Reference
Ref 41	J Med Chem. 1991 May;34(5):1624-30.Synthesis and biological activity of new halo-steroidal antiestrogens. To Reference
Ref 42	J Med Chem. 2009 Dec 10;52(23):7544-69.Identification and structure-activity relationships of chromene-derived selective estrogen receptor modulators for treatment of postmenopausal symptoms. To Reference
Ref 43	Bioorg Med Chem Lett. 2007 Aug 1;17(15):4118-22. Epub 2007 May 23.Bicyclo[2.2.2]octanes: close structural mimics of the nuclear receptor-binding motif of steroid receptor coactivators. To Reference
Ref 44	J Med Chem. 1990 Dec;33(12):3222-9.Structure-activity relationship of antiestrogens. Phenolic analogues of 2,3-diaryl-2H-1-benzopyrans. To Reference
Ref 45	Bioorg Med Chem Lett. 2009 Jan 1;19(1):108-10. Epub 2008 Nov 6.Analogs of methyl-piperidinopyrazole (MPP): antiestrogens with estrogen receptor alpha selective activity. To Reference
Ref 46	J Med Chem. 1998 Jul 30;41(16):2928-31.Discovery and preclinical pharmacology of a novel, potent, nonsteroidal estrogen receptor agonist/antagonist, CP-336156, a diaryltetrahydronaphthalene. To Reference
Ref 47	J Med Chem. 1996 Apr 26;39(9):1778-89.Synthesis and biological activity of novel nonsteroidal progesterone receptor antagonists based on cyclocymopol monomethyl ether. To Reference
Ref 48	J Med Chem. 2001 May 24;44(11):1654-7.Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens. To Reference
Ref 49	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. To Reference
Ref 50	Bioorg Med Chem. 2010 Aug 1;18(15):5593-601. Epub 2010 Jun 20.Genomic action of permanently charged tamoxifen derivatives via estrogen receptor-alpha. To Reference
Ref 51	J Med Chem. 2004 Dec 16;47(26):6435-8.Synthesis and activity of substituted 4-(indazol-3-yl)phenols as pathway-selective estrogen receptor ligands useful in the treatment of rheumatoid arthritis. To Reference
Ref 52	J Med Chem. 1991 Jul;34(7):2145-52.2-Phenylindole-linked [2-(aminoalkyl)pyridine]dichloroplatinum(II): complexes with a selective action on estrogen receptor positive mammary tumors. To Reference
Ref 53	Bioorg Med Chem Lett. 2004 Sep 20;14(18):4659-63.Synthesis and biological evaluation of stilbene-based pure estrogen antagonists. To Reference
Ref 54	EM-800, a novel antiestrogen, acts as a pure antagonist of the transcriptional functions of estrogen receptors alpha and beta. Endocrinology. 1998 Jan;139(1):111-8. To Reference
Ref 55	Molecular mechanism of action at estrogen receptor alpha of a new clinically relevant antiestrogen (GW7604) related to tamoxifen. Endocrinology. 2001 Feb;142(2):838-46. To Reference
Ref 56	Antagonists selective for estrogen receptor alpha. Endocrinology. 2002 Mar;143(3):941-7. To Reference

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