BMS-871: A novel orally active pan-Notch inhibitor as an anticancer agent. Issue 9 (1st May 2015)

• Record Type: Journal Article
• Authors: Shan, Weifang; Balog, Aaron; Quesnelle, Claude; Gill, Patrice; Han, Wen-Ching; Norris, Derek; Mandal, Sunilkumar; Thiruvenkadam, Raja; Gona, Kiran Babu; Thiyagarajan, Kamalraj; Kandula, Sathiah; McGlinchey, Kelly; Menard, Krista; Wen, Mei-Li; Rose, Anne; White, Ronald; Guarino, Victor; Shen, Ding Ren; Cvijic, Mary Ellen; Ranasinghe, Asoka; Dai, Jun; Zhang, Yingru; Wu, Dauh-Rurng; Mathur, Arvind; Rampulla, Richard; Trainor, George; Hunt, John T.; Vite, Gregory D.; Westhouse, Richard; Lee, Francis Y.; Gavai, Ashvinikumar V.;
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 9(2015)
• Page Start: 1905
• Page End: 1909
• Publication Date: 2015-05-01
• Subjects: Anticancer -- Notch inhibitor -- T-acute lymphoblastic leukemia -- Triple-negative breast cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.03.038
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 (compound30 ) which displayed robust in vivo efficacy in Notch-dependent leukemia and solid tumor xenograft models.