Department of Medicinal Chemistry, Genentech, Inc., South San Francisco, CA 94080, USA.
Future Med Chem. 2009 Nov;1(8):1509-25. doi: 10.4155/fmc.09.116.
The inhibitors of apoptosis (IAP) proteins have emerged over the last decade as important targets for therapeutic intervention in human malignancies. Overexpression of IAPs has been implicated in cell survival and resistance against stress-induced apoptosis brought on by radiation and/or chemotherapeutics (currently the standard-of-care in a variety of different cancer diseases). In addition, evasion from death receptor-mediated apoptosis and regulation of NF-κB pathways and cell division have also been associated with IAP proteins. Efforts to target IAP proteins in tumors have focused mainly on designing small molecules that mimic the IAP-binding motif of the endogenous IAP antagonist, second mitochondrial activator of caspases. In addition, several other IAP-targeting strategies, including antisense oligonucleotides and transcriptional repression, have also been initiated, with the hope of providing therapeutic benefit to cancer patients.
凋亡抑制蛋白（IAP）在过去十年中已成为人类恶性肿瘤治疗干预的重要靶点。IAP 的过表达与细胞存活和对辐射和/或化疗药物引起的应激诱导凋亡的抵抗有关（目前是各种不同癌症疾病的标准治疗方法）。此外，逃避死亡受体介导的凋亡以及调节 NF-κB 途径和细胞分裂也与 IAP 蛋白有关。靶向肿瘤中 IAP 蛋白的主要努力集中在设计模拟内源性 IAP 拮抗剂第二线粒体激活的半胱天冬酶（caspase）的 IAP 结合基序的小分子上。此外，还启动了几种其他的 IAP 靶向策略，包括反义寡核苷酸和转录抑制，希望为癌症患者提供治疗益处。
