RT Journal Article
SR Electronic
T1 Identification of the First Synthetic Steroidogenic Factor 1 Inverse Agonists: Pharmacological Modulation of Steroidogenic Enzymes
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 900
OP 908
DO 10.1124/mol.107.040089
VO 73
IS 3
A1 Del Tredici, Andria L.
A1 Andersen, Carsten B.
A1 Currier, Erika A.
A1 Ohrmund, Steven R.
A1 Fairbain, Luke C.
A1 Lund, Birgitte W.
A1 Nash, Norman
A1 Olsson, Roger
A1 Piu, Fabrice
YR 2008
UL http://molpharm.aspetjournals.org/content/73/3/900.abstract
AB Steroidogenic factor SF-1, a constitutively active nuclear hormone receptor, is essential to the development of adrenal and gonadal glands and acts as a shaping factor of sexual determination and differentiation. Its effects are exerted primarily through the control of the synthesis of steroid hormones. The functional cell-based assay Receptor Selection and Amplification Technology (R-SAT) was used to identify potent and selective SF-1 inverse agonists through the screening of a chemical library of drug-like small-molecule entities. Among them, 4-(heptyloxy)phenol (AC-45594), a prototype inverse agonist lead, was used to show that SF-1 constitutive activity can be pharmacologically modulated by a synthetic ligand. In a physiological system of endocrine function, the expression of several reported SF-1 target genes, including SF-1 itself, was inhibited by treatment with AC-45594 and analogs. Thus, pharmacological modulation of SF-1 is critical to its function as an endocrine master regulator and has potentially important consequences to diseases in which SF-1 activity is critical. The American Society for Pharmacology and Experimental Therapeutics