| Literature DB >> 26005526 |
Ashvinikumar V Gavai1, Claude Quesnelle1, Derek Norris1, Wen-Ching Han1, Patrice Gill1, Weifang Shan1, Aaron Balog1, Ke Chen2, Andrew Tebben1, Richard Rampulla1, Dauh-Rurng Wu1, Yingru Zhang1, Arvind Mathur1, Ronald White1, Anne Rose1, Haiqing Wang1, Zheng Yang1, Asoka Ranasinghe1, Celia D'Arienzo1, Victor Guarino1, Lan Xiao1, Ching Su1, Gerry Everlof1, Vinod Arora3, Ding Ren Shen1, Mary Ellen Cvijic1, Krista Menard1, Mei-Li Wen1, Jere Meredith3, George Trainor1, Louis J Lombardo1, Richard Olson3, Phil S Baran2, John T Hunt1, Gregory D Vite1, Bruce S Fischer1, Richard A Westhouse1, Francis Y Lee1.
Abstract
Structure-activity relationships in a series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors of γ-secretase mediated signaling of Notch1/2/3/4 receptors. On the basis of its robust in vivo efficacy at tolerated doses in Notch driven leukemia and solid tumor xenograft models, 12 (BMS-906024) was selected as a candidate for clinical evaluation.Entities:
Keywords: Notch inhibitor; SAR; T-acute lymphoblastic leukemia; triple-negative breast cancer; γ-secretase inhibitor
Year: 2015 PMID： 26005526 PMCID： PMC4434460 DOI： 10.1021/acsmedchemlett.5b00001
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345