| Literature DB >> 26191364 |
Yong Zhang1, Benjamin A Seigal2, Nicholas K Terrett2, Randy L Talbott1, Joseph Fargnoli1, Joseph G Naglich1, Charu Chaudhry1, Shana L Posy1, Ragini Vuppugalla1, Georgia Cornelius1, Ming Lei1, Chunlei Wang1, Yingru Zhang1, Robert J Schmidt1, Donna D Wei1, Michael M Miller1, Martin P Allen1, Ling Li1, Percy H Carter1, Gregory D Vite1, Robert M Borzilleri1.
Abstract
A series of dimeric macrocyclic compounds were prepared and evaluated as antagonists for inhibitor of apoptosis proteins. The most potent analogue 11, which binds to XIAP and c-IAP proteins with high affinity and induces caspase-3 activation and ultimately cell apoptosis, inhibits growth of human melanoma and colorectal cell lines at low nanomolar concentrations. Furthermore, compound 11 demonstrated significant antitumor activity in the A875 human melanoma xenograft model at doses as low as 2 mg/kg on a q3d schedule.Entities:
Keywords: Inhibitor of apoptosis proteins (IAPs); cancer; dimeric macrocyclic antagonists
Year: 2015 PMID： 26191364 PMCID： PMC4499820 DOI： 10.1021/acsmedchemlett.5b00091
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345