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Inhibition of fatty acid synthase (FAS) by the irreversible inhibitor cerulenin leads to cytotoxicity and apoptosis in human cancer cell lines.1 C75 is a more stable inhibitor of FAS than cerulenin that leads to profound weight loss and feeding inhibition in both high-fat diet wild type obese and leptin-deficient ob/ob mice.2 C75 is also cytotoxic to many human cancer cell lines, an effect believed to be mediated by the accumulation of malonyl-coenzyme A in cells with an upregulated FAS pathway.3
1
Moche, M., Schneider, G., Edwards, P., et al. Structure of the complex between the antibiotic cerulenin and its target, β-ketoacyl-acyl carrier protein synthase. J Biol Chem274(10)6031-6034(1999).
2
Loftus, T.M., Jaworsky, D.E., Frehywot, G.L., et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science2882379-2381(2000).
3
Pizer, E.S., Thupari, J., Han, W.F., et al. Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res60213-218(2000).
Room temperature
in continental US; may vary elsewhere
SMILES
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CCCCCCCC[C@H]1OC(=O)C(=C)C1C(=O)O
Background Reading
Moche, M., Schneider, G., Edwards, P., et al. Structure of the complex between the antibiotic cerulenin and its target, β-ketoacyl-acyl carrier protein synthase. J Biol Chem274(10)6031-6034(1999).
Pizer, E.S., Thupari, J., Han, W.F., et al. Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res60213-218(2000).
Loftus, T.M., Jaworsky, D.E., Frehywot, G.L., et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science2882379-2381(2000).
C75 is available in the following screening
library: