NBI 35965 (methanesulfonate)

NBI 35965 methanesulfonate is a selective, orally active and brain-penetrant corticotropin-releasing factor receptor 1 (CRF1) antagonist with a K_i value of 4 nM and a pK_i value of 8.5. NBI 35965 methanesulfonate does not inhibit CRF2. NBI 35965 methanesulfonate reduces CRF or stress-induced adrenocorticotropic hormone (ACTH) production in vivo with pIC₅₀ values of 7.1 and 6.9, respectively. NBI 35965 methanesulfonate shows anxiolytic effects^[1][2]. In Vitro:NBI 35965 methanesulfonate displays a high affinity for CRF1 while having no binding affinity to CRF2. NBI 35965 methanesulfonate also inhibits the stimulation of cAMP induced by Sauvagine in CRF1 transfected cells^[2]. In Vivo:NBI 35965 methanesulfonate (20 mg/kg; oral gavage; once) reduces stress induced ACTH production in mice^[1].
In rats, NBI 35965 methanesulfonate (Compound 12a; 10 mg/kg) has a volume of distribution 17.8 L/kg, a plasma clearance of 17 mL/min/kg, and a half-life of 12 h. The estimated oral bioavailability is 34% with a mean maximal plasma concentration at 1 h of 560 ng/mL. NBI 35965 methanesulfonate also penetrated the blood-brain barrier, resulting in a mean maximal brain concentration of 700 ng/g^[1].