Advances of Research on BIR2-selective Inhibitors of Inhibitor of Apoptosis Proteins
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摘要: 凋亡抑制蛋白XIAP、c-IAP1和c-IAP2是抗肿瘤新药研发的重要靶点，其均含有3个BIR结构域，许多靶向BIR2和BIR3结构域的小分子IAPs抑制剂已被报道，其中BIR2选择性IAPs抑制剂研究相对较少。不同于BIR3选择性IAPs抑制剂，BIR2选择性IAPs抑制剂可以阻断XIAP与Caspase-3和Caspase-7的相互作用，因此是一类具有不同作用机制的新型IAPs抑制剂，对这类化合物的研究对进一步阐明IAPs及IAPs抑制剂的作用机制具有重要意义。综述凋亡抑制蛋白的结构与功能、Smac的功能及其与IAPs的相互作用、BIR2选择性IAPs抑制剂的研究进展，以期为相关研究提供参考。Abstract: XIAP, c-IAP1 and c-IAP2 are important targets for antitumor drug development. They share the common feature of containing three BIR domains. Many small molecule inhibitors targeting the BIR2 and BIR3 domains of these IAPs have been reported with relatively few BIR2-selective IAPs inhibitors. Unlike BIR3-selective IAPs inhibitors, BIR2-selective IAPs inhibitors can block the interaction of XIAP with Caspase-3 and Caspase-7, so they are a new class of IAPs inhibitors with different mechanisms. The study of these compounds is important to further elucidate the mechanisms of action of IAPs and IAPs inhibitors This paper reviews the structure and function of IAPs, the function of Smac and its interaction with IAPs, and the research progress of BIR2-selective IAPs inhibitors, in order to provide some reference for related research.
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Keywords:
- apoptosis /
- IAP /
- caspase /
- protein-protein interaction /
- small molecule inhibitor
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