NBI-42902

NBI-42902 is an orally active, potent functional and competitive antagonist of GnRH receptor with an IC50 value of 0.79 nM, a Ki value of 0.56 nM, respectively. NBI-42902 inhibits GnRH-stimulated inositol phosphate (IP) accumulation, Ca2+ flux, and ERK1/2 activation. NBI-42902 inhibits serum luteinizing hormone (LH) in castrated male macaques. NBI-42902 can be used for research on sex-hormone-related diseases.

NBI-42902 (0-1000 nM) is quite sensitive to the relatively conservative sequence changes between species, with IC₅₀ values of 0.79 nM (human), 10 nM (macaque), 400 nM (dog), 200 nM (rabbit) for the GnRH receptors^[1].
NBI-42902 (1 nM-1 μM, 1 min) inhibits GnRH (4 nM)-stimulated Ca²⁺ flux in RBL cells with a mean IC₅₀ value of 3.6 nM^[1].
NBI-42902 (1 nM-1 μM, 1 min) inhibits GnRH (4 nM)-induced IP accumulation competitively in RBL cells^[1].
NBI-42902 (1 nM-1 μM, 5 min) blocks GnRH-stimulated ERK1/2 phosphorylation completely in CHO-GnRHR cells with an IC₅₀ value of 5.22 nM^[1].

NBI-42902 (10-100 mg/kg, p.o. or i.v. ) inhibits serum LH levels significantly in castrated macaques^[1].

References:
[1]. Struthers RS, et al. Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902. Endocrinology. 2007 Feb;148(2):857-67.