BNS808 is an orally active, selective CB1R antagonist with an IC50 of 0.8 nM, demonstrating significant selectivity for CB2R and minimal brain penetration. It is being studied for the treatment of obesity and related metabolic complications, such as metabolic dysfunction-associated steatotic liver disease (MASLD). BNS808 reduces drug exposure to the central nervous system, enhancing safety, and minimizes drug interactions through high plasma protein binding.

CYP2C9:2.99 μM

BNS808 demonstrates very low cytotoxicity in HepG2 cells over 72 hours, with an IC 50 of 16.84 μM. It has an hERG IC 50 of 5.39 μM, indicating an IC 50 of 0.8 nM for CB 1 R, suggesting low cardiac toxicity potential. At a concentration of 0.2 mg/mL for 10 minutes, BNS808 exhibits moderate inhibition of CYP3A4, weak to moderate inhibition of CYP2C9 and CYP2C19, and weak inhibition of CYP1A2 and CYP2D6, with IC 50 values of 2.99, 8.33, 18.0, and >50 μM, respectively.

Following a single administration, BNS808 (1 mg/kg, oral) exhibited limited brain penetration (average 13.7 ng/g) at various time points (1-8 hours) in C57Bl/6 mice. With prolonged administration of BNS808 (1 mg/kg, oral, 24 days), brain penetration remained limited (approximately 20 ng/g). No central nervous system-mediated side effects or significant changes in motor activity were observed at both low (1 mg/kg) and high (10 mg/kg) doses in wild-type male C57Bl/6J mice. Furthermore, BNS808 (1 mg/kg/day, oral, 24 days) reduced body weight and improved metabolic status in diet-induced obese (DIO) C57Bl/6J mice.