BMS 433796 is a γ-secretase inhibitor that demonstrates Aβ-lowering activity within a transgenic mouse model of Alzheimer's disease.

BMS-433796 causes a concentration-dependent decrease in [3H]IN973 binding, with an IC50 value of 1.2 nM, which is very similar to the IC50 values for the inhibition of Aβ40 (0.8 nM) and Aβ42 (0.4 nM) in human embryonic kidney cells overexpressing the Swedish mutation of APP[1].

Characterized in pharmacokinetic studies in male Sprague-Dawley rats, BMS-433796 shows low clearance with a total body clearance of 5.2±0.82 mL/min/kg (means±SEM; n=3) following a 10-minute intravenous infusion at 2.3 μmol/kg in PEG-400. The apparent terminal elimination half-life is 4.6±0.48 h. Upon oral administration of a PEG-400 suspension at 35 μmol/kg, BMS-433796 exhibits an oral bioavailability of 31% with prolonged absorption. BMS-433796 demonstrates satisfactory metabolic stability in human liver microsomal preparations and is not an inhibitor of human CYPs (IC50>100 μM)[2]. The reduction of brain Aβ40 is dose-dependent upon administering BMS-433796, with an ED50 value of 2.4 mg/kg[1].