PRT062607 Hydrochloride

"目录号: HY-15323

Protein Tyrosine Kinase/RTK-

PRT062607 hydrochloride 是一种有效的纯化的Syk抑制剂，IC50为 1-2 nM。

Syk

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生物活性

Description

PRT062607 hydrochloride is a highly specific and potent inhibitor of purifiedSyk(IC501-2 nM).

IC50& Target

IC50: 1 nM (Syk), 81 nM (Fgr), 88 nM (MLK1), 123 nM (Yes)[1]

In Vitro

PRT062607 (P505-15) Hydrochloride is a novel, highly specific, and potent orally available small-molecule inhibitor of Syk. The potency of PRT062607 against its target kinase Syk is initially tested in two different purified kinase assays. Using a FRET assay, half-maximal Syk inhibition required 6±0.2 nM (mean±S.E.M.). Similar potency is observed when tested in a radioactive enzyme assay, with a resulting Syk IC50of 2.1±0.4 nM (mean±S.E.M.). In human whole blood, PRT062607 potently inhibits B cell antigen receptor-mediated B cell signaling and activation (IC500.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC500.15 μM)[1].

In Vivo

In the mouse CAIA model, oral administration of PRT062607 (P505-15) results in an average inhibition of paw inflammation, as measured by daily scoring of inflammation compared with vehicle controls, of 12, 44, and 87% with average plasma concentration (C average over 24 h) assessed at the end of the study of 0.38, 0.95, and 1.47 μM, respectively. In mice treated with 30 mg/kg PRT062607, the damage to the joints is significantly reduced and seemed indistinguishable from normal mice. In the rat CIA model, the high dose of PRT062607 (15 mg/kg b.i.d.) completely suppresses inflammation in a majority of the animals (seven of eight), by the end of the study (mean inflammation score±S.E.M.=0.63±1.1; p<0.0001 versus vehicle)[1].

References

[1].Coffey G, et al. Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritis. J Pharmacol Exp Ther. 2012 Feb;340(2):350-9.