The present invention is directed to compositions and methods in which a compound interferes, and most typically disrupts or prevents BRCA2/RAD5 1 interaction, and / or RAD5 1 multimerization. Two small compounds with molecular weight about 300-400 were isolated from reverse yeast two hybrid screening using a chemical library containing 30000 compounds. These compounds disrupt the interaction between BRCA2 and Rad51 and lead to sensitive to DNA damage agents such as ionizing radiation or cisplatinim treatment. Therefore, these compounds can be used as drugs for sensitizing cancer cells for chemotherapy.

The inhibitors were tested successfully in CML cell lines, including Imatinib-resistant cell lines. Imatinib is a standard CML treatment; however its activity is limited by frequently developed tumor resistance. The inhibitors successfully reduced or eliminated human breast cancer transplanted into nude mice. Further, the inhibitors were active in mouse model of CML (Bcr-Abl mice). Currently inventors are analyzing combinational treatment of inhibitors with Imatinib to eliminate or delay Imatinib resistance in mice.

File Number: 18782 

Web site: http://techtransfer.universityofcalifornia.edu/...

Disease: Autoimmune and Inflammation