NBI-42902

• CAT Number: I008252
• CAS Number: 352290-60-9
• Molecular Formula: C27H24F3N3O3
• Molecular Weight: 495.49
• Purity: ≥95%
• Synonyms: 3-[(2R)-2-amino-2-phenylethyl]-1-[(2,6-difluorophenyl)methyl]-5-(2-fluoro-3-methoxyphenyl)-6-methylpyrimidine-2,4-dione
• InChI: InChI=1S/C27H24F3N3O3/c1-16-24(18-10-6-13-23(36-2)25(18)30)26(34)33(15-22(31)17-8-4-3-5-9-17)27(35)32(16)14-19-20(28)11-7-12-21(19)29/h3-13,22H,14-15,31H2,1-2H3/t22-/m0/s1
• InChIKey: CJUWBZDJMYYRDG-QFIPXVFZSA-N
• SMILES: CC1=C(C(=O)N(C(=O)N1CC2=C(C=CC=C2F)F)CC(C3=CC=CC=C3)N)C4=C(C(=CC=C4)OC)F

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[1].
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].

Reference

[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.
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