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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 Mcl-1. Here we review the latest progress on the discovery and development of selective inhibitors of Mcl-1 that are undergoing clinical evaluation for cancer therapy.
Hird et al. (Mon,) studied this question.