AdipoRon (SC-396658) is an orally bioavailable adiponectin receptor agonist. It can combine with AdipoR1/2 (KD: 1.8/3.1 μM).

AdipoR2:3.1 μM(Kd), AdipoR1:1.8 μM(Kd)

In wild-type mice, AdipoRon administered orally (50 mg/kg) activates the AdipoR2–PPAR-α pathway in the liver or the AdipoR1–AMPK–PGC-1α pathway in skeletal muscle, thereby improving insulin resistance, lipid abnormalities, and glucose tolerance. In the skeletal muscle and liver of WT mice, AdipoRon (50 mg/kg, intravenously) significantly induces phosphorylation of AMPK via AdipoR1/2. Furthermore, AdipoRon ameliorates diabetic symptoms in the genetic obesity murine model db/db mice and extends the shortened lifespan of db/db mice on a high-fat diet.

AdipoRon, through its interaction with AdipoR1/2 in C2C12 myotubes, enhances the activation of AMPK and promotes the expression of PGC-1α as well as mitochondrial biogenesis.

The effects of AdipoRon on the proliferation of parenchymal and non-parenchymal hepatocytes are evaluated in vitro via L02 and RAW264.7, by MTT assay as described with slight modification: 100 μL cells suspension (6×104/mL) are seeded in a 96-well plate and incubated for 18 h. Fresh media with AdipoRon are added at specified concentrations, and the incubations continue for a further 24 h. Then cells are incubated for 4 h with 0.5 mg/mL of MTT, and analyzed in a microplate reader at 490 nm. Each group is performed in six replications. The mean absorbance values corrected for a blank (medium only) are calculated as percentages of survival.