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TOFA

MCE China：TOFA

Brand：MedChemExpress (MCE)

Cat. No.HY-101068

CAS：54857-86-2

Synonyms：RMI14514; MDL14514

Purity：99.59%

Storage：Powder -20°C 3 years 4°C 2 years In solvent -80°C 1 year -20°C 6 months

Shipping：Room temperature in continental US; may vary elsewhere.

Description：TOFA (RMI14514;MDL14514) is an allosteric inhibitor of acetyl-CoA carboxylase-α (ACCA ).

In Vitro：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[1]. TOFA is found to be cytotoxic to COC1 and COC1/DDP cells with IC50 values of ~26.1 and 11.6 μg/mL, respectively. 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[2]. 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[3].

In Vivo：TOFA inhibits COC1/DDP cell growth in ovarian tumor mouse xenografts. 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. By inhibiting ACC, TOFA may be a promising small molecule agent for ovarian cancer therapy[2].

Animal Administration：Mice: Mice are treated with 50 μL DMSO (control group) or treated with TOFA (50 mg/kg). The drugs are injected intraperitoneally daily for two weeks. Tumor volumes are recorded every two days by measuring dimensions (length and width) with Vernier calipers. The mice are sacrificed four weeks after the final treatment. Tumor weights are measured by a scale[2].

Cell Assay：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].

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References：

[1]. Wang C, et al. Acetyl-CoA carboxylase-alpha inhibitor TOFA induces human cancer cell apoptosis. Biochem Biophys Res Commun. 2009 Jul 31;385(3):302-6.  [Content Brief]

[2]. Li S, et al. TOFA suppresses ovarian cancer cell growth in vitro and in vivo. Mol Med Rep. 2013 Aug;8(2):373-8.  [Content Brief]

[3]. Guseva NV, 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. Cancer Biol Ther. 2011 Jul 1;12(1):80-5.  [Content Brief]