TOFA 是有效的乙酰辅酶A羧化酶-α (ACCA)的变构抑制剂。

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

TOFA inhibits the proliferation of the cancer cells examined in a time and dose dependent manner, arrests the cells in the G0/G1 cell cycle phase and induces apoptosis. Acetyl-CoA-carboxylase-α (ACCA) is a key enzyme in the regulation of fatty acids synthesis. Inhibition of ACCA by TOFA decreases fatty acid synthesis and induces caspase activation and cell death in most PCa cell lines. TOFA (5-tetradecyloxy-2-furoic acid) is cytotoxic to lung cancer cells NCI-H460 and colon carcinoma cells HCT-8 and HCT-15, with an IC50 at approximately 5.0, 5.0, and 4.5 μg/mL, respectively. TOFA at 1.0–20.0 μg/mL effectively blocks fatty acid synthesis and induces cell death in a dose-dependent manner. TOFA is found to be cytotoxic to COC1 and COC1/DDP cells with IC50 values of ~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].

54857-86-2

C19H32O4

324.461

RMI14514;MDL14514

DMSO:34 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years