BMS433796是一种γ-分泌酶抑制剂，用于阿尔茨海默氏病转基因小鼠模型，可降低Aβ活性。
CAS：935525-13-6
分子式：C19H16F2N4O4
分子量：402.35
纯度：98%
存储：Store at -20°C

Background:

BMS 433796 is a γ-secretase inhibitor with Aβ lowering activity in a transgenic mouse model of Alzheimer’s disease.

BMS-433796 cause a concentration-dependent decrease in [3H]IN973 binding, with IC50 value of 1.2 nM, very similar to the IC50 values for inhibition of Aβ40 in human embryonic kidney cells overexpressing the Swedish mutation of APP of 0.8 nM, respectively, and for inhibition of Aβ42 of 0.4 nM, respectively[2].

BMS 433796 is characterized in pharmacokinetic studies in male Sprague-Dawley rats. Following a 10-min intravenous infusion at 2.3 μmol/kg in PEG-400, the total body clearance of 40 is 5.2±0.82 mL/min/kg (means±SEM; n=3), indicating low clearance. The apparent terminal elimination half-life is 4.6±0.48 h. Oral administration of a PEG-400 suspension at 35 μmol/kg shows an oral bioavailability of 31% with prolonged absorption. BMS 433796 has satisfactory metabolic stability in human liver microsomal preparations and is not an inhibitor of human CYPs (IC50>100 μM)[1]. Brain Aβ40 is reduced as a result of administering BMS-433796 in a dose-dependent manner, with ED50 value of 2.4 mg/kg, respectively[2].

[1]. Prasad CV, et al. Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796): a gamma-secretase inhibitor with Abeta lowering activity in a transgenic mouse model of Alzheimer’s disease. Bioorg Med Chem Lett. 2007 Jul 15;17(14):4006-11. [2]. Goldstein ME, et al. Ex vivo occupancy of gamma-secretase inhibitors correlates with brain beta-amyloid peptide reduction in Tg2576 mice. J Pharmacol Exp Ther. 2007 Oct;323(1):102-8.