Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors
Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors
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DOI：
10.1021/acsmedchemlett.5b00001
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发表时间：
2015-05-01
影响因子：
4.2
通讯作者：
Lee, Francis Y.
中科院分区：
文献类型：
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作者：
Gavai, Ashvinikumar V.;Quesnelle, Claude;Lee, Francis Y.
一系列（2-氧代-1，4-苯并二氮杂卓-3-基）-琥珀酰胺的构效关系鉴定了Notch 1/2/3/4受体γ-分泌酶介导信号传导的高效抑制剂。基于其在Notch驱动的白血病和实体瘤异种移植模型中在耐受剂量下的稳健体内疗效，选择12（BMS-906024）作为临床评价的候选药物。
Structure activity relationships in a series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors of gamma-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.