Orlistat (Tetrahydrolipstatin) is a well-known irreversible inhibitor of pancreatic and gastric lipases. Orlistat is also an inhibitor of fatty acid synthase (FASN), is used orally for long-term research of obesity. Anti-atherosclerotic effect.
体外研究
Orlistat (40 μM; 2 days) does not affect MGMT levels in a human melanoma cell line, but downregulates the repair protein by 30-70% in human peripheral blood mononuclear cells, in two leukemia and two colon cancer cell lines. Orlistat does not alter noticeably MGMT mRNA expression.
Western Blot Analysis
Cell Line:
The human melanoma cell line M10, Peripheral blood mononuclear cells , The human Jurkat CD4 T cell leukemia cell line, the human promyelocytic leukemia cell line HL-60, the epithelial colon cancer HCT116 cells,non adherent mononuclear cells (NAMNC)
Concentration:
2.5, 5, 10, 20, 40 μM for Jurkat cells; 20 and 40 μM for HCT116 cells; 40 μM for normal NAMNC, M10 melanoma, HL-60 promyelocytic leukemia, and HT-29 colon cancer cells
Incubation Time:
2 days for Jurkat cells; 2 or 4 days for HCT116 cells; 2 days for NAMNC, M10 melanoma, HL-60 promyelocytic leukemia, HT-29 colon cancer
Result:
Reduced by >50% the MGMT level at the concentration of 40 μM for Jurkat cells, whereas little or no effect was found when lower concentrations were used.
Downregulation of MGMT expression is produced at 40 μM for HCT116 cells.
Provoked an ~50% reduction of MGMT level at 40 μM in normal NAMNC, and HL-60 promyelocytic leukemia, HT-29 colon cancer cells except for melanoma M10 cells that showed no downregulation of the protein.
体内研究
Orlistat (10 mg/kg/day) significantly improves lipid profile, increases antioxidant enzymes and expression of anti-inflammatory markers, and decreases the expression of the pro-inflammatory marker compared to the obese (OB) group.
Animal Model:
Eighteen male rats of Sprague–Dawley strain aged between 8–10 weeks weighing 200-250 g
Dosage:
10 mg/kg/day
Administration:
Orally; six weeks
Result:
Treatment persistently restored the increased body weight, which was significantly observed at the ninth week until the end of the experimental period.
分子式
C29H53NO5
分子量
495.73
CAS号
96829-58-2
中文名称
奥利司他
运输条件
Room temperature in continental US; may vary elsewhere.