AC 45594 is a full inverse agonist of steroidogenic factor 1 (SF-1) with an IC50 value of 50~100 nM [1].
SF-1 is a constitutively nuclear hormone receptor. It is essential to the development of gonadal and adrenal glands. It acts as a shaping factor in sexual differentiation and determination. Its effects are exerted primarily via controlling steroid hormone synthesis [1].
Human adrenocortical H295R/TR SF-1 cells were overexpressing SF-1 in a Dox-inducible fashion. After a 4-day treatment with AC 45594, the proliferation of H295R/TR SF-1 cells cultured in basal conditions was inhibited in a dose-dependent manner. AC 45594 showed maximal effect at 10 µM. SF-1 overexpression induced cell proliferation. In the presence of Dox, incubation with AC 45594 at 1 µM markedly reduced the effect of SF-1 overexpression. Moreover, treatment with AC 45594 increased the percentage of sub-G1 (apoptotic) cells [2]. In human adrenocortical H295 cells, cAMP is able to induce the expression of StAR. This induction is dependent on the presence of SF-1. Incubation with AC 45594 dose-dependently reduced amounts of the StAR mRNA to basal levels. At the protein level, 24 h after the cAMP treatment, StAR was increased by 30-fold. But treatment with AC 45594 completely and dose-dependently reversed the cAMP-dependent activation of StAR [1].
No result regarding the effect of AC 45594 in animal bodies had been found.
References:
[1]. Del Tredici AL, Andersen CB, Currier EA, et al. Identification of the first synthetic steroidogenic factor 1 inverse agonists: pharmacological modulation of steroidogenic enzymes. Molecular pharmacology, 2008, 73(3): 900-908.
[2]. Doghman M, Cazareth J, Douguet D, et al. Inhibition of adrenocortical carcinoma cell proliferation by steroidogenic factor-1 inverse agonists. The Journal of Clinical Endocrinology & Metabolism, 2009, 94(6): 2178-2183.