Application of a Flexible Synthesis of (5 R)-Thiolactomycin To Develop New Inhibitors of Type I Fatty Acid Synthase

…, A Vadlamudi, KI Miller, FP Kuhajda…

Index: McFadden, Jill M.; Medghalchi, Susan M.; Thupari, Jagan N.; Pinn, Michael L.; Vadlamudi, Aravinda; Miller, Katherine I.; Kuhajda, Francis P.; Townsend, Craig A. Journal of Medicinal Chemistry, 2005 , vol. 48, # 4 p. 946 - 961

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Citation Number: 76

Abstract

Fatty acid synthase (FAS) catalyzes the synthesis of palmitate from the sequential condensation of an acetyl primer with two carbon units added from malonyl-CoA. Inhibition of the β-ketoacyl synthase domain of mammalian FAS leads to selective cytotoxicity to various cancer cell lines in vitro and in vivo. Also, inhibitors of FAS can cause reduced food intake and body weight in mice. Naturally occurring thiolactomycin (TLM) was used as a ...