Potency and Selectivity of SMAC/DIABLO Mimetics in Solid Tumor Therapy

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Abstract
Aiming to promote cancer cell apoptosis is a mainstream strategy of cancer therapy. The second mitochondria-derived activator of caspase (SMAC)/direct inhibitor of apoptosis protein (IAP)-binding protein with low pI (DIABLO) protein is an essential and endogenous antagonist of inhibitor of apoptosis proteins (IAPs). SMAC mimetics (SMs) are a series of synthetically chemical compounds. Via database analysis and literature searching, we summarize the potential mechanisms of endogenous SMAC inefficiency, degradation, mutation, releasing blockage, and depression. We review the development of SMs, as well as preclinical and clinical outcomes of SMs in solid tumor treatment, and we analyze their strengths, weaknesses, opportunities, and threats from our point of view. We also highlight several questions in need of further investigation.
Funding Information
  • National Natural Science Foundation of China (31771582, 31271445)
  • Natural Science Foundation of Guangdong Province (2017A030313131)
  • “Thousand, Hundred, and Ten” project of the Department of Education of Guangdong Province of China (124)
  • Basic and Applied Research Major Projects of Guangdong Province of China (2017KZDXM035, 2018KZDXM036)
  • “Yang Fan” Project of Guangdong Province of China (Andy T. Y. Lau-2016, Yan-Ming Xu-2015)

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