ATGL Inhibitor, Atglistatin-Calbiochem

C₁₇H₂₁N₃O

283.37

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.

Cell permeable: yes
Primary Target
ATGL
Reversible: yes

Toxicity: Standard Handling (A)

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

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

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

100

≥97% (HPLC)

powder

700 nM IC₅₀
355 nM K_i

Calbiochem^®

OK to freeze
protect from light

beige

DMSO: 100 mg/mL

2-8℃

Packaged under inert gas

11 - Combustible Solids

WGK 3