Benzopyrans Are Selective Estrogen Receptor β Agonists with Novel Activity in Models of Benign Prostatic Hyperplasia

• Published in: Journal of medicinal chemistry Vol. 49; no. 21; pp. 6155 - 6157
• Main Authors: Norman, Bryan H, Dodge, Jeffrey A, Richardson, Timothy I, Borromeo, Peter S, Lugar, Charles W, Jones, Scott A, Chen, Keyue, Wang, Yong, Durst, Gregory L, Barr, Robert J, Montrose-Rafizadeh, Chahrzad, Osborne, Harold E, Amos, Robert M, Guo, Sherry, Boodhoo, Amechand, Krishnan, Venkatesh
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 19.10.2006; Amer Chemical Soc
• Subjects: Animals; Binding Sites; Biological and medical sciences; Chemistry, Medicinal; Crystallography, X-Ray; Estrogen Receptor alpha - chemistry; Estrogen Receptor beta - agonists; Estrogen Receptor beta - chemistry; Estrogens; Flavonoids - chemical synthesis; Flavonoids - chemistry; Flavonoids - pharmacology; Hormones. Endocrine system; Humans; Life Sciences & Biomedicine; Ligands; Male; Medical sciences; Mice; Models, Molecular; Molecular Structure; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Prostate - drug effects; Prostate - pathology; Prostatic Hyperplasia - drug therapy; Prostatic Hyperplasia - pathology; Science & Technology; Selective Estrogen Receptor Modulators - chemical synthesis; Selective Estrogen Receptor Modulators - chemistry; Selective Estrogen Receptor Modulators - pharmacology; Structure-Activity Relationship; Urinary system; POTENT; ER-BETA; LIGANDS; MOUSE; FINASTERIDE; ALPHA; RAT PROSTATE; DISCOVERY; STRUCTURE-BASED DESIGN; Agonist; Urinary system disease; Prostate disease; Rodentia; Oral administration; Selectivity; In vitro; Biological activity; Estrogen receptor β; In vivo; Vertebrata; Mammalia; Mouse; Animal; Phenols; Benign prostatic hyperplasia; Models; Benign neoplasm; Chemical synthesis; Male genital diseases; Hormonal receptor
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm060491j

Benzopyran selective estrogen receptor beta agonist-1 (SERBA-1) shows potent, selective binding and agonist function in estrogen receptor β (ERβ) in vitro assays. X-ray crystal structures of SERBA-1 in ERα and β help explain observed β-selectivity of this ligand. SERBA-1 in vivo demonstrates involution of the ventral prostate in CD-1 mice (ERβ effect), while having no effect on gonadal hormone levels (ERα effect) at 10× the efficacious dose, consistent with in vitro properties of this molecule.