1NDE

Estrogen Receptor beta with Selective Triazine Modulator

Summary for 1NDE

• Entry DOI: 10.2210/pdb1nde/pdb
• Descriptor: Estrogen receptor beta, 4-(2-{[4-{[3-(4-CHLOROPHENYL)PROPYL]SULFANYL}-6-(1-PIPERAZINYL)-1,3,5-TRIAZIN-2-YL]AMINO}ETHYL)PHENOL (3 entities in total)
• Functional Keywords: estrogen receptor, estrogen receptor beta, er, erb, triazine, estrogen, estradiol, oestrogen, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q92731
• Total number of polymer chains: 1
• Total formula weight: 29595.60

Authors

Henke, B.R.,Consler, T.G.,Go, N.,Hale, R.L.,Hohman, D.R.,Jones, S.A.,Lu, A.T.,Moore, L.B.,Moore, J.T.,Orband-Miller, L.A.,Robinett, R.G.,Shearin, J.,Spearing, P.K.,Stewart, E.L.,Turnbull, P.S.,Weaver, S.L.,Williams, S.P.,Wisely, G.B.,Lambert, M.H. (deposition date: 2002-12-09, release date: 2002-12-18, Last modification date: 2023-08-16)

Primary citation

Henke, B.R.,Consler, T.G.,Go, N.,Hale, R.L.,Hohman, D.R.,Jones, S.A.,Lu, A.T.,Moore, L.B.,Moore, J.T.,Orband-Miller, L.A.,Robinett, R.G.,Shearin, J.,Spearing, P.K.,Stewart, E.L.,Turnbull, P.S.,Weaver, S.L.,Williams, S.P.,Wisely, G.B.,Lambert, M.H.
A New Series of Estrogen Receptor Modulators That Display Selectivity for Estrogen Receptor beta
J.Med.Chem., 45:5492-5505, 2002

PubMed Abstract: A series of 1,3,5-triazine-based estrogen receptor (ER) modulators that are modestly selective for the ERbeta subtype are reported. Compound 1, which displayed modest potency and selectivity for ERbeta vs ERalpha, was identified via high-throughput screening utilizing an ERbeta SPA-based binding assay. Subsequent analogue preparation resulted in the identification of compounds such as 21 and 43 that display 25- to 30-fold selectivity for ERbeta with potencies in the 10-30 nM range. These compounds profile as full antagonists at ERbeta and weak partial agonists at ERalpha in a cell-based reporter gene assay. In addition, the X-ray crystal structure of compound 15 complexed with the ligand binding domain of ERbeta has been solved and was utilized in the design of more conformationally restrained analogues such as 31 in an attempt to increase selectivity for the ERbeta subtype.

PubMed: 12459017
DOI: 10.1021/jm020291h

Experimental method

X-RAY DIFFRACTION (3 Å)