TOFA (MDL14514) is an allosteric inhibitor of acetyl-CoA carboxylase-α (ACCA).

TOFA (5-tetradecyloxy-2-furoic acid) inhibits cancer cell proliferation by inducing apoptosis, arresting cells in the G0/G1 phase, and showing time and dose-dependent cytotoxic effects. It targets Acetyl-CoA-carboxylase-α (ACCA), leading to reduced fatty acid synthesis, caspase activation, and cell death, particularly in prostate cancer (PCa) cells. TOFA exhibits significant cytotoxicity in lung cancer cells NCI-H460 and colon carcinoma cells HCT-8 and HCT-15, with IC50 values of around 5.0, 5.0, and 4.5 μg/mL, respectively. Concentrations from 1.0 to 20.0 μg/mL block fatty acid synthesis and induce cell death dose-dependently. It is also cytotoxic to COC1 and COC1/DDP cells, with IC50 values of approximately 26.1 and 11.6 μg/mL, respectively.

The tumor growth rate is signifi?cantly inhibited by TOFA compared with the DMSO treated control mice (1649±356.3 vs. 5128±390.4 mm3. No toxicity is observed in the heart, liver, spleen, lung, kidney and intestinal tissues. TOFA inhibits COC1/DDP cell growth in ovarian tumor mouse xenografts. By inhibiting ACC, TOFA may be a promising small molecule agent for ovarian cancer therapy.

NCI-H460, human lung cancer cells, and HCT-8 and HCT-15 cells (5,000/well) are seeded in 96-well plates overnight and then exposed to TOFA at indicated concentrations (0, 1, 5, 10, 20, 50 μg/mL) for 72 hours. Viable cells are detected using MTT assay[1].