Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors

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 xenogra...

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Published in:ACS medicinal chemistry letters 2015-05, Vol.6 (5), p.523-527
Main Authors: Gavai, Ashvinikumar V, Quesnelle, Claude, Norris, Derek, Han, Wen-Ching, Gill, Patrice, Shan, Weifang, Balog, Aaron, Chen, Ke, Tebben, Andrew, Rampulla, Richard, Wu, Dauh-Rurng, Zhang, Yingru, Mathur, Arvind, White, Ronald, Rose, Anne, Wang, Haiqing, Yang, Zheng, Ranasinghe, Asoka, D’Arienzo, Celia, Guarino, Victor, Xiao, Lan, Su, Ching, Everlof, Gerry, Arora, Vinod, Shen, Ding Ren, Cvijic, Mary Ellen, Menard, Krista, Wen, Mei-Li, Meredith, Jere, Trainor, George, Lombardo, Louis J, Olson, Richard, Baran, Phil S, Hunt, John T, Vite, Gregory D, Fischer, Bruce S, Westhouse, Richard A, Lee, Francis Y
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Language:English
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Summary: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.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.5b00001