From Wikipedia, the free encyclopedia
Chemical compound
Β-LGND2 |
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Other names | β-LGND2; ER-β-selective ligand 2 |
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Drug class | Nonsteroidal estrogen; Selective ERβ agonist |
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4-bromo-6,8-dihydroxy-2-(4-hydroxyphenyl)isoquinolin-1-one
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CAS Number | |
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PubChem CID | |
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CompTox Dashboard (EPA) | |
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Formula | C15H10BrNO4 |
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Molar mass | 348.152 g·mol−1 |
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3D model (JSmol) | |
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C1=CC(=CC=C1N2C=C(C3=CC(=CC(=C3C2=O)O)O)Br)O
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InChI=1S/C15H10BrNO4/c16-12-7-17(8-1-3-9(18)4-2-8)15(21)14-11(12)5-10(19)6-13(14)20/h1-7,18-20H Key:GLVQMSCCFOGRRG-UHFFFAOYSA-N
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β-LGND2, also known as ERβ-selective ligand 2 or as GTx-878, is a synthetic nonsteroidal estrogen and selective ERβ agonist which was under development by GTx for the treatment of benign prostatic hyperplasia, prostatitis, and rheumatoid arthritis but was never marketed.[1][2][3][4][5][6] It shows approximately 25-fold selectivity for activation of the ERβ over the ERα (EC50Tooltip half-maximal effective concentration = 2 nM and 52 nM, respectively).[3] β-LGND2 is an isoquinolinone derivative.[2][5]
- ^ "Research programme: Estrogen receptor beta agonists - Oncternal Therapeutics - AdisInsight".
- ^ a b Yepuru M, Eswaraka J, Kearbey JD, Barrett CM, Raghow S, Veverka KA, Miller DD, Dalton JT, Narayanan R (October 2010). "Estrogen receptor-{beta}-selective ligands alleviate high-fat diet- and ovariectomy-induced obesity in mice". J. Biol. Chem. 285 (41): 31292–303. doi:10.1074/jbc.M110.147850. PMC 2951204. PMID 20657011.
- ^ a b Ponnusamy S, Tran QT, Harvey I, Smallwood HS, Thiyagarajan T, Banerjee S, Johnson DL, Dalton JT, Sullivan RD, Miller DD, Bridges D, Narayanan R (January 2017). "Pharmacologic activation of estrogen receptor β increases mitochondrial function, energy expenditure, and brown adipose tissue". FASEB J. 31 (1): 266–281. doi:10.1096/fj.201600787RR. PMC 5161516. PMID 27733447.
We found that β-LGND2, also known as GTx-878 (GTx, Inc. (31)), reduces body weight and fat mass without altering feed consumption of high-fat diet (HFD)-fed WT, but not ER-βKO, mice.
- ^ Giddabasappa A, Eswaraka JR, Barrett CM, Bauler MN, Wu Z, Yepuru M, Miller DD, Dalton JT (July 2012). "β-LGND2, an ERβ selective agonist, inhibits pathologic retinal neovascularization". Invest. Ophthalmol. Vis. Sci. 53 (8): 5066–75. doi:10.1167/iovs.12-9627. PMID 22714897.
- ^ a b Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F (November 2014). "Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential". Steroids. 90: 13–29. doi:10.1016/j.steroids.2014.06.012. PMC 4192010. PMID 24971815.
- ^ Mohler ML, Narayanan R, Coss CC, Hu K, He Y, Wu Z, Hong SS, Hwang DJ, Miller DD, Dalton JT (April 2010). "Estrogen receptor beta selective nonsteroidal estrogens: seeking clinical indications". Expert Opin Ther Pat. 20 (4): 507–34. doi:10.1517/13543771003657164. PMID 20302450. S2CID 314347.
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ERTooltip Estrogen receptor | Agonists |
- Steroidal: 2-Hydroxyestradiol
- 2-Hydroxyestrone
- 3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol
- 3α-Androstanediol
- 3α,5α-Dihydrolevonorgestrel
- 3β,5α-Dihydrolevonorgestrel
- 3α-Hydroxytibolone
- 3β-Hydroxytibolone
- 3β-Androstanediol
- 4-Androstenediol
- 4-Androstenedione
- 4-Fluoroestradiol
- 4-Hydroxyestradiol
- 4-Hydroxyestrone
- 4-Methoxyestradiol
- 4-Methoxyestrone
- 5-Androstenediol
- 7-Oxo-DHEA
- 7α-Hydroxy-DHEA
- 7α-Methylestradiol
- 7β-Hydroxyepiandrosterone
- 8,9-Dehydroestradiol
- 8,9-Dehydroestrone
- 8β-VE2
- 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED)
- 11β-Chloromethylestradiol
- 11β-Methoxyestradiol
- 15α-Hydroxyestradiol
- 16-Ketoestradiol
- 16-Ketoestrone
- 16α-Fluoroestradiol
- 16α-Hydroxy-DHEA
- 16α-Hydroxyestrone
- 16α-Iodoestradiol
- 16α-LE2
- 16β-Hydroxyestrone
- 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol)
- 17α-Estradiol (alfatradiol)
- 17α-Dihydroequilenin
- 17α-Dihydroequilin
- 17α-Epiestriol (16α-hydroxy-17α-estradiol)
- 17α-Ethynyl-3α-androstanediol
- 17α-Ethynyl-3β-androstanediol
- 17β-Dihydroequilenin
- 17β-Dihydroequilin
- 17β-Methyl-17α-dihydroequilenin
- Abiraterone
- Abiraterone acetate
- Alestramustine
- Almestrone
- Anabolic steroids (e.g., testosterone and esters, methyltestosterone, metandienone (methandrostenolone), nandrolone and esters, many others; via estrogenic metabolites)
- Atrimustine
- Bolandiol
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- Butolame
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- Epimestrol
- Equilenin
- Equilin
- ERA-63 (ORG-37663)
- Esterified estrogens
- Estetrol
- Estradiol
- Estramustine
- Estramustine phosphate
- Estrapronicate
- Estrazinol
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- Estrofurate
- Estrogenic substances
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- Estrone
- Etamestrol (eptamestrol)
- Ethinylandrostenediol
- Ethinylestradiol
- Ethinylestriol
- Ethylestradiol
- Etynodiol
- Etynodiol diacetate
- Hexolame
- Hippulin
- Hydroxyestrone diacetate
- Lynestrenol
- Lynestrenol phenylpropionate
- Mestranol
- Methylestradiol
- Moxestrol
- Mytatrienediol
- Nilestriol
- Norethisterone
- Noretynodrel
- Orestrate
- Pentolame
- Prodiame
- Prolame
- Promestriene
- RU-16117
- Quinestradol
- Quinestrol
- Tibolone
- Xenoestrogens: Anise-related (e.g., anethole, anol, dianethole, dianol, photoanethole)
- Chalconoids (e.g., isoliquiritigenin, phloretin, phlorizin (phloridzin), wedelolactone)
- Coumestans (e.g., coumestrol, psoralidin)
- Flavonoids (incl. 7,8-DHF, 8-prenylnaringenin, apigenin, baicalein, baicalin, biochanin A, calycosin, catechin, daidzein, daidzin, ECG, EGCG, epicatechin, equol, formononetin, glabrene, glabridin, genistein, genistin, glycitein, kaempferol, liquiritigenin, mirificin, myricetin, naringenin, penduletin, pinocembrin, prunetin, puerarin, quercetin, tectoridin, tectorigenin)
- Lavender oil
- Lignans (e.g., enterodiol, enterolactone, nyasol (cis-hinokiresinol))
- Metalloestrogens (e.g., cadmium)
- Pesticides (e.g., alternariol, dieldrin, endosulfan, fenarimol, HPTE, methiocarb, methoxychlor, triclocarban, triclosan)
- Phytosteroids (e.g., digitoxin (digitalis), diosgenin, guggulsterone)
- Phytosterols (e.g., β-sitosterol, campesterol, stigmasterol)
- Resorcylic acid lactones (e.g., zearalanone, α-zearalenol, β-zearalenol, zearalenone, zeranol (α-zearalanol), taleranol (teranol, β-zearalanol))
- Steroid-like (e.g., deoxymiroestrol, miroestrol)
- Stilbenoids (e.g., resveratrol, rhaponticin)
- Synthetic xenoestrogens (e.g., alkylphenols, bisphenols (e.g., BPA, BPF, BPS), DDT, parabens, PBBs, PHBA, phthalates, PCBs)
- Others (e.g., agnuside, rotundifuran)
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Mixed (SERMsTooltip Selective estrogen receptor modulators) | |
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Antagonists |
- Coregulator-binding modulators: ERX-11
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GPERTooltip G protein-coupled estrogen receptor | Agonists | |
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Antagonists | |
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Unknown | |
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