JD-5037 is a novel, peripherally restricted CB1R antagonist with an IC50 of 1.5 nM.

JD5037, when administered at a dosage of 3 mg/kg/day intraperitoneally (i.p.), effectively induces uniform reductions in body weight and mitigates high-fat diet (HFD)-induced hyperglycemia, hepatic injury, and steatosis in obese Magel2-null mice. Likewise, oral administration of JD5037 (3 mg/kg/day, p.o.) significantly diminishes tumor size and eliminates tumors in DEN-treated mice. Moreover, JD5037 reduces anandamide (AEA) levels in hepatocellular carcinoma (HCC) samples from mice.

Mice: JD-5037 is formulated in vehicle (V; 1% Tween80, 4% DMSO, 95% Saline). Obese mice are treated chronically (28 d) with vehicle (V; 1% Tween80, 4% DMSO, 95% Saline), JD5037, or SLV319 at a dose of 3 mg/kg, i.p. Body weight and food intake are monitored daily. Mice are euthanized by cervical dislocation under anesthesia; the brain, hypothalamus, liver, and combined fat pads are removed, weighed, and snap-frozen, and trunk blood is collected for determining the endocrine and biochemical parameters