Discovery of Potent Heterodimeric Antagonists of Inhibitor of Apoptosis Proteins (IAPs) with Sustained Antitumor Activity

作者：Perez Heidi L^*; Chaudhry Charu; Emanuel Stuart L; Fanslau Caroline; Fargnoli Joseph; Gan Jinping; Kim Kyoung S; Lei Ming; Naglich Joseph G; Traeger Sarah C; Vuppugalla Ragini; Wei Donna D; Vite Gregory D; Talbott Randy L; Borzilleri Robert M

来源：Journal of Medicinal Chemistry, 2015, 58(3): 1556-1562.

DOI：10.1021/jm50182t

The prominent role of IAPs in controlling cell death and their overexpression in a variety of cancers has prompted the development of IAP antagonists as potential antitumor therapies. We describe the identification of a series of heterodimeric antagonists with highly potent antiproliferative activities in cIAP- and XIAP-dependent cell lines. Compounds 15 and 17 further demonstrate curative efficacy in human melanoma and lung cancer xenograft models and are promising candidates for advanced studies.

• 出版日期2015-2-12