BMS-871: A novel orally active pan-Notch inhibitor as an anticancer agent

Abstract This Letter describes synthesis, SAR, and biological activity of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides as inhibitors of γ-secretase mediated signaling of Notch receptors. Optimization of this series led to the identification of BMS-871 (compound 30 ) which displayed robust in vivo efficacy in Notch-dependent leukemia and solid tumor xenograft models.