TOFA

TOFA (5-tetradecyloxy-2-furoic acid) is an endogenous small molecule, as an allosteric agent, which targets Acetyl-CoA carboxylase (ACC) [1].

ACC is a rate-limiting enzyme in fatty acid metabolism, which catalyzes the carboxylation of Acetyl-CoA to malonyl-CoA in an ATP-dependent way.

Inhibition of acetyl-CoA carboxylase-α (ACCA) treated by TOFA decreased fatty acid synthesis and induced caspase activation and cell death in most PCa cell lines. Besides, TOFA induced cell apoptosis via the mitochondrial pathway in androgen-sensitive cell lines by inducing the release of cytochrome c from mitochondria [2].

Rats were fed diets containing varying concentrations of TOFA or clofibrate for 4-10 days. Compared with untreated control rats, TOFA produced a dose-dependent reduction of plasma cholesterol levels, which achieved a higher reduction at 583 μmol/kg/day than 40% reduction treated by clofibrate in a dose range of 766-1693 μmol/kg/day [1].

Reference:

[1] Parker R A, Kariya T, Grisar J M. Petrow V. 5-(Tetradecyloxy)-2-furancarboxylic acid and related hypolipidemic fatty acid-like alkyloxyarylcarboxylic acids [J]. J Med Chem. 1977, 20(6): 781–791.

[2] Guseva N V, Rokhin O W, Glover R A, et al. TOFA (5-tetradecyl-oxy-2-furoic acid) reduces fatty acid synthesis, inhibits expression of AR, neuropilin-1 and Mcl-1 and kills prostate cancer cells independent of p53 status [J]. Cancer Biol Ther. 2011, 12(1): 80-85.