Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. It inhibits gastric and pancreatic lipases in the lumen of the gastrointestinal tract to decrease systemic absorption of dietary fat. Orlistat treatment also results in modest improvements in total cholesterol, low-density lipoprotein, blood pressure, and fasting glucose and insulin concentrations[3]. The use of orlistat has been associated with rare cases of acute kidney injury. Orlistat has a beneficial effect on carbohydrate metabolism. Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness[4]. Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract. An extremely low degree of systemic absorption for orlistat when administered with a hypocaloric, well-balanced diet with 20% to 30% of calories derived from fat (50-80 gm). Systemic absorption of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition[5]. When orlistat was administered in the early stage of AKT/c-Met-triggered hepatocarcinogenesis, it resulted in the elimination of hepatic tumor burden. Mechanistically, orlistat efficiently elevated PTEN expression and suppressed AKT/SREBP1/FASN (fatty acid synthase) signaling both in vivo and in vitro, impairing AKT/c-Met-driven de novo lipogenesis and aberrant proliferation[6].
Orlistat 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
COS7 cells
Function assay
Inhibition of human recombinant DAGLalpha overexpressed in african green monkey COS7 cells, IC50=0.06 μM
18657971
HEK293T cell
Function assay
Inhibition of human DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate in detergent free solution by FRET assay, IC50=0.01 μM
22738638
HepG2 (DPX-2) cells
Function assay
24 h
Activation of human PXR expressed in human HepG2 (DPX-2) cells assessed as induction of CYP3A4 after 24 hrs by luminescent analysis, EC50=28.2 μM
20966043
MDA-MB-435 cells
Cytotoxicity assay
48 h
Cytotoxicity against human MDA-MB-435 cells after 48 hrs by Cell titer assay, IC50=16.8 μM
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