AdipoR Agonist, AdipoRon

A cell-permeable benzylpiperidinyl-acetamide compound that acts as an adiponectin receptor agonist (K_D = 1.8 µM and 3.1 µM, respectively, in binding studies using human AdipoR1 or AdipoR2; K_D = 6.9 µM and 6.0 µM, respectively, using hepatocytes from AdipoR1^+/+AdipoR2^-/- or AdipoR1^-/-AdipoR2^+/+ mice), effectively stimulating AMPK α-subunit Thr172 phosphorylation in murine myoblast C2C12 cultures (1 to 50 µM; 5 min) in vitro and in skeletal muscle and liver tissues in mice (50 mg/kg i.v.) in vivo without affecting mitochondrial complex I activity. Oral administration (Plasma C_max/T_max post 50 mg/kg oral dosing = 11.8 µM/40 min) in either db/db or high-fat diet-induced wt obese mice (for 10 d to 2 wks) is reported to increase insulin sensitivity and glucose tolerance via activation of AdipoR1-mediated AMPK pathway in muscle and liver, as well as AdipoR2-mediated PPAR-α pathway in liver, resulting in enhanced exercise endurance and prolonged lifespan. In addition to muscle mitochondrial biogenesis enhancement and liver gluconeogenesis inhibition, reduced oxidative stress in calf muscle, liver, and white adipose tissue (WAT), as well as reduced expressions of pro-inflammatory cytokines in liver and WAT are also observed in AdipoRon-treated obese mice in vivo.

A cell-permeable benzylpiperidinyl-acetamide compound that acts as an adiponectin receptor agonist (K_D = 1.8 µM and 3.1 µM, respectively, toward human AdipoR1 and AdipoR2; K_D = 6.9 µM and 6.0 µM, respectively, toward murine AdipoR1 and AdipoR2), effectively stimulating AMPK α-subunit Thr172 phosphorylation in murine myoblast C2C12 cultures (1 to 50 µM; 5 min) in vitro and in skeletal muscle & liver tissues in mice (50 mg/kg i.v.) in vivo. Oral administration in either db/db or high-fat diet-induced wt obese mice (50 mg/kg/d for 10 d to 2 wks) is reported to increase insulin sensitivity and glucose tolerance via activation of AdipoR1-mediated AMPK pathway in muscle & liver, as well as AdipoR2-mediated PPAR-α pathway in liver in vivo, resulting in enhanced exercise endurance and prolonged lifespan.

Cell permeable: yes

Primary Target
AdipoR1 and AdipoR2

Reversible: yes

Target K_i: 1.8 and 3.1 µM

Packaged under inert gas

Toxicity: Standard Handling (A)

Okada-Iwabu, M., et al. 2013. Nature503, 493.

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