New Non-toxic Compounds that Sensitize Cells for DNA Damage Agents and Serving as Adjuvants in Chemotherapy of Cancer
University of California System: University of California, Irvine
posted on 06/16/2009
BRCA2/RAD5 1 interaction is essential for DNA repair mechanisms and play significant role in tumor resistance to irradiation and chemotherapy treatments. Effective strategies to selectively interfere with BRCA2/RAD5 1 interaction in the context of treatment and chemoprevention of neoplastic diseases are described.
Adjutants in chemotherapy of cancer, specifically tested in CML and Leukemia.
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
Disease: Autoimmune and Inflammation
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