TOFA (5-(Tetradecyloxy)-2-furoic acid)

TOFA (5-(Tetradecyloxy)-2-furoic acid) is a cell-permeable small molecule, functional as an inhibitor of fatty acid synthesis through inhibition of acetyl-CoA carboxylase (ACC). Inhibition of this enzyme reduces the availability of endogenous fatty acids for generation of phosphatidylcholine, the major phospholipid in cell membranes. Blockage of ACC also depletes malonyl-CoA levels, indicated to serve a proapoptotic role in cell regulation, and reduction of malonyl-CoA related to TOFA inhibition is reported to confer survival to cancer cells treated with a cytotoxin. TOFA is also described to stimulate citrate accumulation in the cell, which leads to a suppression of glycolysis by citrate-induced inhibition of phosphofructokinase.