ATGL INHIBITOR ATGLISTATIN (C15-1305-006)

General description

A cell-permeable biphenyldimethyl urea compound that inhibits adipose triglyceride lipase (ATGL) activity (IC₅₀ = 700 nM; [Substrate] = [Triolein] = 165 µM) in a substrate-competitive (K_i = 355 nM) and highly selective manner, exhibiting little potency against hormone-sensitive lipase (HSL), monoglyceride lipase (MGL), pancreatic lipase, lipoprotein lipase, or lysophospholipases PNPLA6/7 even at concentrations as high as 100 µM. Shown to effectively suppress FA/glycerol productions from adipocytes (IC_max = 50 to 100 µM in 3T3-L1-differentiated adipocytes or primary murine white adipose tissue/WAT cultures) in vitro and in blood of mice in vivo via either oral or intraperitoneal administration (ED_max = 200 µmol/kg) without affecting plasma glucose, total cholesterol, insulin, or β-hydroxybutyrate (beta-HB) level. Significant cytotoxicity is reported at concentrations >50 µM in AML-12 murine hepatocyte cultures. Although ATGL deficiency causes cardiomyopathy in human and ATGL-ko animals due to severe triacylglycerol (TG) accumulation in cardiac muscle, significant atglistatin level (>0.2 nmol/g tissue) is only seen in liver, white and brown adipose tissues, and detectable TG accumulation is only observed in liver tissue in wt mice 8 h post single 200 µmol/kg oral dosage.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
ATGL

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Mayer, N., et al. 2013. Nat. Chem. Biol.9, 785.

Produced under the license of University of Graz/Graz University of Technology

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Molecular Weight: 283.37. Empirical Formula: C₁₇H₂₁N₃O. Assay: ≥. 97% (HPLC). Quality Level: 100. form: powder. potency: 700 . nM IC₅₀, 355 . nM K_i. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: beige. solubility: DMSO: 100 . mg/mL. storage temp.: 2-8°C. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.