NBI-34041

**NBI-34041** is a small molecule nonpeptide antagonist of the corticotropin-releasing factor 1 (CRF1) receptor with high affinity and selectivity over CRF2. Developed by Neurocrine Biosciences and synthesized as compound 12t, it demonstrates competitive functional antagonism, inhibiting sauvagine-stimulated cAMP accumulation (IC50 ~60 nM) and CRF-stimulated ACTH release in human and rat cells. Preclinical studies in rats showed dose-dependent attenuation of CRF-induced and stress-induced ACTH elevation following oral administration. In a Phase I clinical trial with 24 healthy males dosed at 10-100 mg/day for 14 days, it was safe, did not impair basal HPA axis function or CRF-evoked responses, but attenuated neuroendocrine responses to psychosocial stress (Trier Social Stress Test), supporting its potential for depression and anxiety disorders.[1][3]

Other names

2-(2,4-dichlorophenyl)-4-methyl-6-(1-propyl-butyl)-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene