Structure-Based Approach for Discovery of Small Molecule Inhibitors Targeted at AKT
Abstract
AKT/PKB represents potentially a promising molecular target for the design of new anticancer therapies for the treatment of human breast cancer and other types of cancer. In this DOD Idea Award grant, using computational approach, we have discovered a class of potent small-molecule inhibitor of AKT/PKB (API-59). API-59 selectively inhibits AKT activity and has little effect on other upstream protein kinases or MAP kinases. API-59 is highly potent and effective in inhibition of cell growth and induces apoptosis in human breast cancer cell lines with high levels of AKT and has selectivity over cancer cells with low levels of AKT. Importantly, API-59 has little toxicity to normal cells. Our present study provides a solid proof-of-the-concept that targeting AKT or AKT pathway in human breast cancer is a promising strategy for the design and development of a class of anticancer therapy, and API-59 represents a promising lead compound for further evaluation and optimization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA466577
Entities
People
- Shaomeng Weng
Organizations
- University of Michigan