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Atglistatin

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Atglistatin Basic information

Product Name:
Atglistatin
Synonyms:
  • Atglistatin
  • Atglistatin, >=98%
  • 3-(4'-(dimethylamino)-[1,1'-biphenyl]-3-yl)-1,1-dimethylurea
  • Atglistatin N'-[4'-(Dimethylamino)[1,1'-biphenyl]-3-yl]-N,N-dimethylurea
  • N'-[4'-(Dimethylamino)[1,1'-biphenyl]-3-yl]-N,N-dimethylurea Atglistatin
  • 3-(4'-(DIMETHYLAMINO)BIPHENYL-3-YL)-1,1-DIMETHYLUREA
  • N'-[4'-(Dimethylamino)[1,1'-biphenyl]-3-yl]-N,N-dimethylurea
  • CS-1024
CAS:
1469924-27-3
MF:
C17H21N3O
MW:
283.37
EINECS:
200-256-5
Product Categories:
  • Inhibitors
Mol File:
1469924-27-3.mol
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Atglistatin Chemical Properties

Boiling point:
498.6±45.0 °C(Predicted)
Density 
1.135±0.06 g/cm3(Predicted)
storage temp. 
2-8°C
solubility 
Soluble in DMSO (up to 5 mg/ml) or in Ethanol (up to 5 mg/ml with warming)
form 
powder
pka
15.01±0.70(Predicted)
color 
white to beige
Stability:
Stable for 2 years as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
InChI
1S/C17H21N3O/c1-19(2)16-10-8-13(9-11-16)14-6-5-7-15(12-14)18-17(21)20(3)4/h5-12H,1-4H3,(H,18,21)
InChIKey
AWOPBSAJHCUSAS-UHFFFAOYSA-N
SMILES
CN(C)C(NC1=CC=CC(C2=CC=C(N(C)C)C=C2)=C1)=O
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Safety Information

Hazard Codes 
Xn
Risk Statements 
22-36/37/38
Safety Statements 
36/37/39
WGK Germany 
WGK 3
Storage Class
11 - Combustible Solids
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Atglistatin Usage And Synthesis

Description

Adipose triglyceride lipase (ATGL or PNPLA2) catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets, generating diacylglyerol. Atglistatin is a potent, selective, and competitive inhibitor of ATGL (IC50 = 0.7 μM). It does not inhibit hormone-sensitive lipase, monoglyceride lipase, pancreatic lipase, lipoprotein lipase, or other lysophospholipases. Atglistatin blocks lipolysis by ATGL in vitro, in white adipose tissue organ cultures, and in vivo. It does not affect lipolysis in ATGL knockout mice.

Uses

Atglistatin has been used as a selective inhibitor of adipose triglyceride lipase (ATGL).

Biochem/physiol Actions

Atglistatin is the first selective inhibitor of adipose triglyceride lipase (ATGL), the rate limiting enzyme involved in the mobilization of fatty acids from cellular triglyceride stores. Atglistatin has an IC50 of 0.7 μM in E.coli and no activity against monoglycerol lipase (MGL), hormone-sensitive lipase (HSL), or pancreatic lipase and lipoprotein lipase PNPLA6 and PNPLA7. ATGL generates diacylglycerol from cellular triglyceride stores, which is then degraded by hormone-sensitive lipase (HSL) and monoglyceride lipase into glycerol and fatty acids, promoting the synthesis of lipotoxic metabolites that have been associated with the development of insulin resistance. Atglistatin inhibition of ATGL has been shown to reduce fatty acid mobilization in vitro and in vivo.

in vivo

Animals receive Atglistatin dissolved in olive oil by oral gavage. After application, blood and tissues are collected for determination of plasma parameters, tissue Triacylglycerol (TG) levels, and inhibitor concentrations. Time-course experiments revealed that the lipolytic parameters fatty acids (FA) and glycerol are reduced 4 and 8 hours after application and returned to normal after 12 hours. Eight hours after treatment, a dose-dependent decrease is observed in FA and glycerol levels up to 50% and 62%, respectively. Atglistatin also caused a strong reduction in plasma TG levels (-43%) while blood glucose, total cholesterol, ketone bodies, and insulin levels do not significantly change. Dose and time-dependent inhibition of lipolysis is also observed in response to intraperitoneal injection of Atglistatin[1].

References

[1] NICOLE MAYER. Development of small-molecule inhibitors targeting adipose triglyceride lipase[J]. Nature chemical biology, 2013, 9 12: 785-787. DOI:10.1038/nchembio.1359
[2] RACHID ZAGANI. Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells.[J]. Oncotarget, 2015: 28282-28295. DOI:10.18632/oncotarget.5061

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