Autotaxin converts lysophosphatidylcholine to lysophosphatidic acid (LPA), which can mediate changes in cell proliferation, angiogenesis, and cytokine secretion.1 PF-8380 is a potent inhibitor of autotaxin (IC50 = 2.8 nM in an enzyme assay), the enzyme that converts lysophosphatidylcholine to lysophosphatidic acid (LPA).1 It reverses MMP-13 expression induced by leptin in human OA chondrocytes when used at a concentration of 10 ?M.2 PF-8380 (30 mg/kg) reduces LPA production by >95% following carrageenan-induced inflammation in rats and inhibits autotaxin activity in human whole blood (IC50 = 101 nM).1
1.Gierse, J., Thorarensen, A., Beltey, K., et al.A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammationJ. Pharmacol. Exp. Ther.334(1)310-317(2010) 2.Datta, P., Zhang, Y., Parousis, A., et al.High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signatureSci. Rep.7(1)8205(2017)