TOFA
Inhibition of fatty acid synthase (FASN) by the irreversible inhibitor cerulenin leads to cytotoxicity and apoptosis in human cancer cell lines.{11992} TOFA is an inhibitor of fatty acid synthesis blocking the synthesis of malonyl-CoA by acetyl-CoA carboxylase (ACC).{7659} Both cerulenin (at about 10 µg/ml) and TOFA (at about 1 µg/ml) are effective at blocking the incorporation of radiolabeled acetate into palmitate. However, TOFA reduces malonyl-CoA levels rather than elevating them, and TOFA is relatively non-toxic to various cancer cell lines. TOFA also attenuates the inhibition of feeding observed when FASN inhibitors such as cerulenin and C75 are administered to obese ob/ob mice.
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