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Data Show SuperGen's Multi-Targeted Tyrosine Kinase Inhibitor,Suppresses Critical Double-Stranded DNA Repair Protein, Rad51

al of MP470," said Dr. James S. Manuso, SuperGen's Chairman, President and Chief Executive Officer. "Our products and programs were highlighted in seven posters and a mini-symposium. The data presented brings to light important new aspects of our late-stage preclinical compounds and also validates CLIMB as a rapid and powerful process for the identification of a broad range of potent small molecule inhibitors."

Abstract No. 4028

MP470, a potent suppressor of Rad51, improves response to platinum-based anticancer agents

Rad51 is an important protein involved in resistance to cytotoxic/DNA damaging therapies that are commonly used to treat tumors. It acts to repair the double stranded DNA breaks that are caused by therapies, thus limiting their efficacy and increasing dosage requirements. Data indicate that SuperGen's novel compound, MP470, blocks the induction of Rad51 by anticancer platinum agents. MP470, in combination with carboplatin and paclitaxel in small cell and non-small cell lung cancer lines, showed a significant improvement in tumor response over the carboplatin/paclitaxel treatments alone. A combination therapy regimen that includes MP470 in addition to a platinum-based cytotoxic agent could reduce dosage requirements and widen the therapeutic window.

Abstract No. 1540

Hydrochloride salt of MP470, a potent suppressor of Rad51, improves bioavailability and tolerability

Results from this study suggest that the hydrochloride salt of MP470 (MP470.HCl) could lead to improved safety and tolerability of the compound. Data indicate that MP470.HCl exhibits a several-fold improvement in oral bioavailability when compared to the free base. The compound had a wide therapeutic window in rat and dog models. Additionally, no apparent serious toxicities in the expected therapeutic dose range were observed.

Abstract No. 2380

Discovery and characterization of a series of Axl kinase inhibitors using the CLIMB process'"/>




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