Zhao Jiang-Ting, Zheng Xiang, Rao Guo-Wu, Zheng Quan
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou310014, P. R. China.
Core Facility, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, P. R. China.
Curr Med Chem. 2024 May 20. doi: 10.2174/0109298673283734240206020150.
Inhibitors of Apoptosis Proteins (IAP) are inhibitors that can block programmed cell death, are expressed at high levels in various cancers, and are recognized as a therapeutic target for cancer therapy. In the past few years, several small molecule IAP protein inhibitors have been designed to mimic the endogenous IAP antagonist, but no IAP inhibitors have been approved for marketing worldwide. Previously, xevinapant has been awarded a breakthrough therapy designation by the FDA. In addition, a combination of Smac-mimetics and chemotherapeutic compounds has been reported to improve anticancer efficacy. According to the phase II clinical data, xevinapant has the potential to significantly enhance the standard therapy for patients with head and neck cancer, which is expected to be approved as an innovative therapy for cancer patients. Therefore, this paper briefly describes the mechanism of IAPs (AT-406, APG-1387, GDC- 0152, TL32711, and LCL161) as single or in combination for cancer treatment, their application status as well as the synthetic pathway, and explores the research prospects and challenges of IAPs antagonists in the tumor combination therapy, with the hope of providing strong insights into the further development of Smac mimics in tumor therapy.
凋亡抑制蛋白（IAP）是一类能够阻断程序性细胞死亡的抑制剂，在多种癌症中高表达，被公认为癌症治疗的一个靶点。在过去几年中，人们设计了几种小分子IAP蛋白抑制剂来模拟内源性IAP拮抗剂，但尚无IAP抑制剂在全球获批上市。此前，希维纳潘已获得美国食品药品监督管理局（FDA）授予的突破性疗法认定。此外，据报道，Smac模拟物与化疗化合物联合使用可提高抗癌疗效。根据II期临床数据，希维纳潘有可能显著增强头颈癌患者的标准治疗效果，有望获批成为癌症患者的创新疗法。因此，本文简要介绍了IAPs（AT-406、APG-1387、GDC-0152、TL32711和LCL161）单药或联合用于癌症治疗的作用机制、应用现状以及合成途径，并探讨IAP拮抗剂在肿瘤联合治疗中的研究前景与挑战，以期为Smac模拟物在肿瘤治疗中的进一步发展提供有力参考。
