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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 TOFA is an inhibitor of fatty acid synthesis acting one step earlier in the metabolic pathway, blocking the synthesis of malonyl-CoA by acetyl-CoA carboxylase (ACC).2 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 FAS inhibitors such as cerulenin and C75 are administered to obese ob/ob mice.
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).
Synonyms
RMI 14514
5-(Tetradecyloxy)-2-furoic Acid
Formal Name
5-(tetradecyloxy)-2-furancarboxylic acid
CAS Number
54857-86-2
Molecular Formula
C19H32O4
Formula Weight
324.5
Formulation
A crystalline solid
Purity
≥98%
λmax
278 nm
Stability
2 years
Storage
-20°C
Shipping
Room temperature
in continental US; may vary elsewhere
SMILES
Copy SMILES to clipboard
CCCCCCCCCCCCCCOc1ccc(o1)C(=O)O
Background Reading
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).
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).
TOFA is available in the following screening
library: