SYNTHESIS AND ANTITUMOR EVALUATION OF CC1065 ANALOGS

点击翻译按钮获取中文摘要

CC-1065 analogs are among the most potent anti-cancer drugs discovered and have unique mechanisms of antitumor action. Derivatives of CC-1065 lacking its delayed toxicity have significant antitumor activity in clinical trials. However, suppression on human bone marrow undermines their clinical effectiveness. Two new racemic CC-1065 analogs, YW-200 and YW-213 show remarkable antitumor activity in vivo without causing myelosuppression, the dose-limiting toxicity for other CC-1065 analogs. We propose to synthesize and evaluate natural enantiomeric (+)-YW-200 and (+)-YW-201, a precursor to YW-213. (+)-YW-200 and (+)-YW-201 will have improved antitumor efficacy with fewer side-effects. The overall goal of phase II is pre-clinical development with the ultimate goal of filing an IND. PROPOSED COMMERCIAL APPLICATIONS: A novel class of anti-cancer drugs has a substantial and growing market.