CST, 47750S, TOFA

Chemical Modulators for studying in the research area. Product Usage Information TOFA is supplied as a lyophilized powder. For a 15 mM stock, reconstitute 5 mg of powder in 1.03 mL of DMSO. Working concentrations and length of treatment can vary depending on the desired effect. Storage Store lyophilized at -20ºC, desiccated. In lyophilized form, the chemical is stable for 24 months. Once in solution, store at -20ºC and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles . Background The small-molecule TOFA is an allosteric inhibitor of acetyl-CoA carboxylase-α (ACC), which catalyzes carboxylation of acetyl-CoA to malonyl-CoA in cells. It is the key enzyme in the biosynthesis and oxidation of fatty acids (1). Conversion of TOFA to an acetyl-CoA analog (TOFyl-CoA) that cannot be further metabolized to malonyl-CoA creates an allosteric inhibitor of ACC (2). Because many cancer cells require fatty acids for high metabolic needs and rapid proliferation, the reduction of ACC activity is a common target in limiting cancer cell growth. TOFA treatment of lung cancer and colon carcinoma cells blocked fatty acid synthesis, and increased fatty acid oxidation and ketogenesis, inducing apoptosis and cell death (3). Exposure of human pancreatic cancer cells to TOFA resulted in fatty acid depletion, increased caspase-3 activity, and induced cell death (4). TOFA treatment of human renal cell carcinoma inhibited cell growth and arrested cell cycle at G2/M phase, leading to apoptosis (5). Alternate Names 5-(Tetradecyloxy)-2-furoic acid; RMI-14514