PF-8380 is a potent autotaxin inhibitor with an IC(50) of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood. PF-8380 has adequate oral bioavailability and exposures required for in vivo testing of autotaxin inhibition. Autotaxin's role in producing LPA in plasma and at the site of inflammation was tested in a rat air pouch model. The specific inhibitor PF-8380 , dosed orally at 30 mg/kg, provided >95% reduction in both plasma and air pouch LPA within 3 h, indicating autotaxin is a major source of LPA during inflammation. At 30 mg/kg PF-8380 reduced inflammatory hyperalgesia with the same efficacy as 30 mg/kg naproxen.
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Roflumilast; Sildenafil citrate; Cilomilast; Tadalafil; Pimobendan; GSK256066; Mardepodect; Rolipram; Apremilast; Milrinone; Avanafil; Ziritaxestat; Ibudilast; Balipodect; Deltarasin; Anagrelide hydrochloride; Enpp-1-IN-1; Crisaborole; CP671305