Journal
PHARMACOLOGY & THERAPEUTICS
Volume 198, Issue -, Pages 59-67Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2019.02.007
Keywords
Apoptosis; Protein-protein interactions; Mcl-1; BH-3 mimetic drugs; Drug development; Cancer
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Dysregulation of the mitochondrial apoptotic pathway controlled by members of the Bcl-2 protein family plays a central role in cancer development and resistance to conventional cytotoxic as well as targeted therapies. Hence, selective inhibition of pro-survival Bcl-2 family of proteins to activate apoptosis in malignant cells represents an exciting anti-cancer strategy. The remarkable clinical performance of the selective Bcl-2 antagonist venetoclax has highlighted the potential for selective inhibitors of the other pro-survival members of the Bcl-2 family, particularly Mc1-1. Here we review the latest progress on the discovery and development of selective inhibitors of Mc1-1 that are undergoing clinical evaluation for cancer therapy. (C) 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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