【摘 要】
：
Epothilones, 16-member ring macrolides, originally isolated from myxobacterium Sorangium cellulosum in soil were shown to exert potent cytotoxicity via stabilization of microtubule polymerization, lik
【机 构】
：
Preclinical Pharmacology Core Laboratory Memorial Sloan-Kettering Cancer Center New York USA
【出 处】
：
BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
论文部分内容阅读
Epothilones, 16-member ring macrolides, originally isolated from myxobacterium Sorangium cellulosum in soil were shown to exert potent cytotoxicity via stabilization of microtubule polymerization, like Taxol(R).They are not cross-resistant to multi-drug resistance drugs.At MSKCC, we have synthesized over 100 epothilones through pharmacology directed de novo total synthesis via molecular design of new pharmacophores.The third generation epothilone, iso-oxazole-fludelone (Iso-flu) is 20-and 1,000-fold more potent than Taxol against CCRF-CEM and CCRF-CEM/Taxol cell growth, respectively.It is not only with enhanced potency and solubility, but also with markedly improved metabolic stability and tumor penetrating capabilities.It has been shown that it achieved "Therapeutic cure" (> 10-log cell kill or no relapse from complete remission (CR) for over 10% of life-span) against human mammary MX-1, ovarian SK-OV-3, colon HCT-116, and leukemic CCRF-CEM xenograft tumors [Chou et al, PNAS USA 105:13157-13162, 2008].
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