Lipase Inhibitor, THL (Tetrahydrolipstatin), is a compound that has been shown to rapidly inactivate lipoprotein lipase (LPL). This agent has been found to bind both subunits of LPL, induce tetramerisation, and cause local conformational changes. The exception to lipase inhibition capacities of THL is phospholipase A2, which is not affected by THL. Mechanistic studies suggest that THL inhibits the thioesterase domain of fatty acid synthase (FAS) and as a result halts cell proliferation and causes cell apoptosis. More detailed experiments show that gradually THL affects the retinoblastoma protein pathway and leads to cell-cycle arrest at G1/S boundary. Lipase Inhibitor, THL is an inhibitor of pancreatic and gastric lipase, as well as carboxyl ester lipase (CEL) and diacylglycerol lipase-α (DAGLα). Lipase Inhibitor, THL also activates caspase-3.
1. Lookene, A., et al. 1994. Eur. J. Biochem. 222: 395-403. PMID: 8020477 2. Sternby, B., et al. 2002. Clin Nutr. 21: 395-402. PMID: 12381337 3. Kridel, S.J., et al. 2004. Cancer Res. 64: 2070-2075. PMID: 15026345 4. Knowles, L.M., et al. 2004. J. Biol. Chem. 279: 30540-30545. PMID: 15138278
Soluble in DMSO (19 mg/mL), ethanol (20 mg/mL), and DMF (20 mg/mL).
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MalviMalvi, P. et al. (PubMed 25499031) found that Orlistat, an inhibitor of pancreatic and gastric lipase, and an activator of caspase-3, treatment and dietary intervention reversed rapid melanoma progression induced by obesity. -SCBT Publication Review
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