Molecular Modulation of Inhibitors of Apoptosis as a Novel Approach for Radiosensitization of Human Prostate Cancer
Abstract
The major goal of the project is to investigate the radiosensitization activity and mechanism of action of novel IAP-inhibitors in prostate cancer. We have investigated the in vitro radiosensitization activity of our lead IAP-inhibitors, SH-130 and Embelin, in human prostate cancer cell lines. IAP-inhibitors potently enhanced TRAIL-/radiation-induced apoptosis and growth inhibition. Using NMR and Crystal Structure Analysis, we conclusively show that these IAP inhibitors bind to the pocket in the XIAP BIR3 domain where Smac binds. Biotin-labeled SH-130 pull-down assay further confirm that BIR3 domain in XIAP and cIAP-1 is indeed the molecular target of the IAP inhibitors in apoptosis-potentiation. Based on our exciting data obtained from this PCRP project, together with data from other collaborators, we are working with FDA for ND filing aiming for Phase I clinical trial with SH-130 as radiosensitizer for prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2006
- Accession Number
- ADA462392
Entities
People
- Liang Xu
Organizations
- University of Michigan