Journal
APPLIED SCIENCES-BASEL
Volume 11, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/app11010335
Keywords
inhibitor of apoptosis proteins (IAPs); Smac; DIABLO; LCL161; birinapant; GDC-0152
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Funding
- Ministry of Science and Technology, Taiwan [MOST 109-2320-B006-031]
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This article reviews the anti-cancer potency and novel molecular targets of Smac mimetics, highlighting their ability to induce apoptosis, arrest cell cycle, induce necroptosis, and trigger an immune response. Clinical trials have evaluated the safety and effectiveness of Smac mimetics, with promising results when combined with chemotherapy compounds. Recent studies have uncovered new anti-cancer mechanisms of Smac mimetics, indicating further exploration is needed for potential modification and combination therapies.
Inhibitor of apoptosis proteins (IAPs) are suggested as therapeutic targets for cancer treatment. Smac/DIABLO is a natural IAP antagonist in cells; therefore, Smac mimetics have been developed for cancer treatment in the past decade. In this article, we review the anti-cancer potency and novel molecular targets of LCL161, birinapant, and GDC-0152. Preclinical studies demonstrated that Smac mimetics not only induce apoptosis but also arrest cell cycle, induce necroptosis, and induce immune storm in vitro and in vivo. The safety and tolerance of Smac mimetics are evaluated in phase 1 and phase 2 clinical trials. In addition, the combination of Smac mimetics and chemotherapeutic compounds was reported to improve anti-cancer effects. Interestingly, the novel anti-cancer molecular mechanism of action of Smac mimetics was reported in recent studies, suggesting that many unknown functions of Smac mimetics still need to be revealed. Exploring these currently unknown signaling pathways is important to provide hints for the modification and combination therapy of further compounds.
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