中文同义词:
5-(十四烷氧基)-2-糠酸;乙酰辅酶A羧化酶-Α(ACCA)变构抑制剂(TOFA);5-(十四烷基氧)-2-糠酸;化合物TOFA
英文名称:
5-(TETRADECYLOXY)-2-FUROIC ACID
英文同义词:
TOFA;5-(tetradecyloxy)-2-furancarboxylicaci;5-tetradecyloxy-2-furonicacid;mdl14514;RMI-14514;TOFA (5-(Tetradecyloxy)-2-furoic acid);5-(TETRADECYLOXY)-2-FURANCARBOXYLIC ACID;5-(TETRADECYLOXY)-2-FUROIC ACID
应用
5-(十四烷基氧)-2-糠酸可作为有机合成中间体和医药中间体，可用于实验室研发过程和化工医药生产过程中。
生物活性
TOFA (5-(Tetradecyloxy)-2-furoic acid, Tyrphostin 46,Tyrphostin A46,Tyrphostin B40)是acetyl-CoA carboxylase-α (ACCA)的变构抑制剂。在细胞内TOFA转化为TOFyl-CoA (5-tetradecyloxy-2-furoyl-CoA)，对ACCA具有变构抑制作用。 TOFA阻止脂肪酸合成，并以剂量依赖性方式诱导细胞死亡。
体外研究
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 IC 50 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 IC 50 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. 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.
体内研究
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 mm 3 . 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.
