产品说明书

Orlistat

Print
Chemical Structure| 96829-58-2 同义名 : Tetrahydrolipstatin;Ro-18-0647;Orlistat, Alli, Tetrahydrolipastatin, Tetrahydrolipstatin, THLP, Xenical;(–)-Tetrahydrolipstatin;Ro 18-0647/002
CAS号 : 96829-58-2
货号 : A512085
分子式 : C29H53NO5
纯度 : 98%
分子量 : 495.735
MDL号 : MFCD05662360
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(211.81 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5% DMSO+40% PEG 300+5% Tween 80+water 13 mg/mL

生物活性
靶点

  • Lipase
描述 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].
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
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.02mL

0.40mL

0.20mL

10.09mL

2.02mL

1.01mL

20.17mL

4.03mL

2.02mL
参考文献

[1]Cioccoloni G, Bonmassar L, et al. Influence of fatty acid synthase inhibitor orlistat on the DNA repair enzyme O6-methylguanine-DNA methyltransferase in human normal or malignant cells in vitro. Int J Oncol. 2015 Aug;47(2):764-72.

[2]Kridel SJ, Axelrod F, et al. Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res. 2004 Mar 15;64(6):2070-5.

[3]Heck AM, Yanovski JA, Calis KA. Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000 Mar;20(3):270-9

[4]Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS. Orlistat-associated adverse effects and drug interactions: a critical review. Drug Saf. 2008;31(1):53-65

[5]Zhi J, Melia AT, Eggers H, Joly R, Patel IH. Review of limited systemic absorption of orlistat, a lipase inhibitor, in healthy human volunteers. J Clin Pharmacol. 1995 Nov;35(11):1103-8

[6]Zhang C, Sheng L, Yuan M, Hu J, Meng Y, Wu Y, Chen L, Yu H, Li S, Zheng G, Qiu Z. Orlistat delays hepatocarcinogenesis in mice with hepatic co-activation of AKT and c-Met. Toxicol Appl Pharmacol. 2020 Apr 1;392:114918