BMS-767778

BMS-767778 is an orally active and selective DPP4 inhibitor with K_i values of 0.94 nM, 4.9, 3.2 nM for DPP4, DPP8 and DPP9 respectively. BMS-767778 exhibits >3,000-fold selectivity over the related enzymes DPP8 and DPP9. BMS-767778 inhibits CYP-3A4 with IC₅₀ of 5.2 μM. BMS-767778 significantly reduces blood glucose levels in high fat fed (HFD) ob/ob mice with safety profile. BMS-767778 can be used for diabetes mellitus research^[1].
IC50 & Target:Kis: 0.9 nM (DPP4), 4.9 μM (DPP8), 3.2 μM (DPP9)^[1]. In Vitro:BMS-767778 (compound 2s) exhibits good passive membrane permeability, with PAMPA effective permeability (P_e) values of 19.7, 129.7, and 330 × 10^-6 cm/s at pH 5.5, 6.5, and 7.4, respectively^[1].
BMS-767778 displays an efflux ratio (basolateral-to-apical / apical-to-basolateral permeability) of greater than 5 in Caco-2 cell assays (at pH > 6.5)^[1].
BMS-767778 exhibits low plasma protein binding across species: 18% (human), 14% (mouse), 28% (rat), 27% (dog), and 16% (monkey) ^[1].
BMS-767778 demonstrates a low metabolic turnover in both liver microsomes and hepatocytes, and correspondingly, a low hepatic clearance is predicted in humans^[1].
In Vivo:BMS-767778 (compound 2s) (0.15-5.0 mg/kg, o.p., once) significantly reduces blood glucose levels in high fat fed (HFD) ob/ob mice^[1].
BMS-767778 (500 mg/kg, o.p., once) results no clinical chemistry or hemotology changes in rats^[1].
BMS-767778 (300 mg/kg, o.p., 14 days) results no clinical chemistry or hemotology changes in rats^[1].
BMS-767778 (25 mg/kg, o.p., 5 days) produces no significant changes in dogs^[1].
BMS-767778 (50 mg/kg, o.p., 5 days) results a softening of stools in dog^[1].
BMS-767778 (50 mg/kg) not demonstrate any potential for undesirable cardiovascular activity^[1].