Arhalofenate

Arhalofenate is an orally bioavailable prodrug form of the free acid form of a peroxisome proliferator-activated receptor γ (PPARγ) partial agonist.¹ It is converted to the active free acid form by nonspecific serum esterases. Arhalofenate has weak PPARγ transactivation activity in a reporter assay but strong transrepression activity, reducing LPS-induced chemokine (C-C motif) ligand 2 (CCL2) secretion in isolated mouse peritoneal macrophages. It reduces fasting plasma glucose levels in ob/ob mouse and Zucker diabetic fatty (ZDF) rat models of type 2 diabetes when administered at doses of 125 and 100 mg/kg, respectively. It also decreases fasting free fatty acid, triglyceride, and cholesterol levels in ZDF rats without increasing body weight when administered at a dose of 100 mg/kg.² Arhalofenate (250 mg/kg) prevents leukocyte and neutrophil infiltration and IL-1β, IL-6, and chemokine (C-X-C motif) ligand 1 (CXCL1) production in air pouch fluid in a mouse model of gout.³

WARNING This product is not for human or veterinary use.

1. Gregoire, F.M., Zhang, F., Clarke, H.J., et al. MBX-102/JNJ39659100, a novel peroxisome proliferator-activated receptor-ligand with weak transactivation activity retains antidiabetic properties in the absence of weight gain and edema. Mol. Endocrinol. 23(7), 975-988 (2009).

2. Chandalia, A., Clarke, H.J., Clemens, L.E., et al. MBX-102/JNJ39659100, a novel non-TZD selective partial PPAR-γ agonist lowers triglyceride independently of PPAR-α activation. PPAR Res. 706852 (2009).

3. McWherter, C., Choi, Y.-J., Serrano, R.L., et al. Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling. Arthritis Res. Ther. 20(1), 204 (2018).