Structural highlights
Function
[ESR2_HUMAN] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
A new series of estrogen receptor modulators that display selectivity for estrogen receptor beta.,Henke BR, Consler TG, Go N, Hale RL, Hohman DR, Jones SA, Lu AT, Moore LB, Moore JT, Orband-Miller LA, Robinett RG, Shearin J, Spearing PK, Stewart EL, Turnbull PS, Weaver SL, Williams SP, Wisely GB, Lambert MH J Med Chem. 2002 Dec 5;45(25):5492-505. PMID:12459017[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Henke BR, Consler TG, Go N, Hale RL, Hohman DR, Jones SA, Lu AT, Moore LB, Moore JT, Orband-Miller LA, Robinett RG, Shearin J, Spearing PK, Stewart EL, Turnbull PS, Weaver SL, Williams SP, Wisely GB, Lambert MH. A new series of estrogen receptor modulators that display selectivity for estrogen receptor beta. J Med Chem. 2002 Dec 5;45(25):5492-505. PMID:12459017
