Background:

3-Thiatetradecanoic Acid is an activator of PPAR.

The peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in fatty acid metabolism and energy homeostasis. The PPARs also play crucial roles in the control of cellular growth and differentiation.

In vitro: In BT4Cn cells, 3-thiatetradecanoic acid could activate all PPAR subtypes dose-dependently. In cell culture experiments, the PPARγ-selective ligand BRL49653 moderately inhibited growth of BT4Cn cells, while administration of 3-thiatetradecanoic acid led to a marked growth inhibition. Moreover, the administration of the PPARγ-selective antagonist GW9662 abolished BRL49653-induced growth inhibition, but only marginally reduced the effect of 3-thiatetradecanoic acid [1].

In vivo: Administration of 3-thiatetradecanoic acid increased mitochondrial and peroxisomal beta-oxidative capacity and carnitine palmitoyltransferase activity, but reduced free fatty acid and triacylglycerol levels in plasma compared to palmitic acid-treated rats and controls. 3-Thiatetradecanoic acid administration was able to affect the fatty acid composition in plasma and liver by increasing the amount of monoenes [2].

Clinical trial: A previous study described the clinical, hematological, and biochemical safety of 3-thiatetradecanoic acid. 3-Thiatetradecanoic acid was given as a single oral dose for 7 consecutive days. No significant changes were observed in the hematological or clinical chemical parameters in blood/urine. 3-Thiatetradecanoic acid did not induce significant changes in the blood lipids or free fatty acids, but it did lead to an increase in plasma concentration of Δ9 desaturated 3-thiatetradecanoic acid. 3-thiatetradecanoic acid was found to be safe and well tolerated [3].

参考文献:
1.  Berge K, Tronstad KJ, Flindt EN, Rasmussen TH, Madsen L, Kristiansen K, Berge RK. Tetradecylthioacetic acid inhibits growth of rat glioma cells ex vivo and in vivo via PPAR-dependent and PPAR-independent pathways. Carcinogenesis. 2001 Nov;22(11):1747-55.
2.  Asiedu, D.K.,Froyland, L.,Vaagenes, H., et al. Long-term effect of tetradecylthioacetic acid: A study on plasma lipid profile and fatty acid composition and oxidation in different rat organs. Biochimica et Biophysica Acta 1300, 86-96 (1996)._x000B_3. Pettersen RJ, Salem M, Skorve J, Ulvik RJ, Berge RK, Nordrehaug JE. Pharmacology and safety of tetradecylthioacetic acid (TTA): phase-1 study. J Cardiovasc Pharmacol. 2008 Apr;51(4):410-7.