Orally administered PRT062607 in the CAIA mouse model demonstrates a dose-dependent reduction in paw inflammation, with inflammation scores decreasing by 12%, 44%, and 87% at plasma concentrations of 0.38, 0.95, and 1.47 μM, respectively. At a dosage of 30 mg/kg, PRT062607 notably diminishes joint damage, making it virtually undetectable compared to that in normal mice. In the rat CIA model, a high dose (15 mg/kg b.i.d.) of PRT062607 fully alleviates inflammation in most subjects (seven out of eight), resulting in a significantly low average inflammation score ^[1].

PRT062607 (P505-15) is a novel, highly specific, and potent orally available small-molecule inhibitor of Syk. A FRET assay demonstrates a half-maximal inhibition concentration for Syk at 6±0.2 nM, with a similar inhibitory capacity observed in a radioactive enzyme test, showing a Syk IC50 of 2.1±0.4 nM. In human whole blood, PRT062607 effectively blocks B cell antigen receptor-driven B cell signaling and activation (with IC50 values of 0.27 and 0.28 μM, respectively) and inhibits Fcε receptor 1-triggered basophil degranulation (IC50 of 0.15 μM)^[1].