1. AZD4320, A Dual Inhibitor of Bcl-2 and Bcl-x
- Author
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Srividya B, Balachander, Steven W, Criscione, Kate F, Byth, Justin, Cidado, Ammar, Adam, Paula, Lewis, Terry, Macintyre, Shenghua, Wen, Deborah, Lawson, Kathleen, Burke, Tristan, Lubinski, Jeffrey W, Tyner, Stephen E, Kurtz, Shannon K, McWeeney, Jeffrey, Varnes, R Bruce, Diebold, Thomas, Gero, Stephanos, Ioannidis, Edward J, Hennessy, William, McCoull, Jamal C, Saeh, Areya, Tabatabai, Omid, Tavana, Nancy, Su, Alwin, Schuller, Mathew J, Garnett, Patricia, Jaaks, Elizabeth A, Coker, Gareth P, Gregory, Andrea, Newbold, Ricky W, Johnstone, Eric, Gangl, Martin, Wild, Michael, Zinda, J Paul, Secrist, Barry R, Davies, Stephen E, Fawell, and Francis D, Gibbons
- Subjects
bcl-X Protein ,Antineoplastic Agents ,Apoptosis ,Mice, SCID ,Thrombocytopenia ,Xenograft Model Antitumor Assays ,Mice ,Piperidines ,Proto-Oncogene Proteins c-bcl-2 ,Mice, Inbred NOD ,Hematologic Neoplasms ,Benzamides ,Tumor Cells, Cultured ,Animals ,Humans ,Female ,Sulfones ,Cell Proliferation - Abstract
Targeting Bcl-2 family members upregulated in multiple cancers has emerged as an important area of cancer therapeutics. While venetoclax, a Bcl-2-selective inhibitor, has had success in the clinic, another family member, Bcl-xWe used structure-based chemistry to design a small-molecule inhibitor of Bcl-2 and Bcl-xWe discovered AZD4320, which has nanomolar affinity for Bcl-2 and Bcl-xAZD4320 is a potent molecule with manageable thrombocytopenia risk to explore the utility of a dual Bcl-2/Bcl-x
- Published
- 2020