PRT-060318 (PRT318) is a novel selective inhibitor of the tyrosine kinase Syk with an IC₅₀ of 4 nM.

PRT318 is a potent inhibitor of purified Syk kinase with an IC₅₀ of 4 nM. Syk kinase is inhibited by 92%, whereas all other kinases retains more than 70% at a concentration of 50 nM of PRT318. PRT318 and P505-15 effectively antagonize CLL cell survival after B-cell receptor (BCR) triggering and in nurse-like cell-co-cultures. They inhibit BCR-dependent secretion of the chemokines CCL3 and CCL4 by CLL cells, and leukemia cell migration toward the tissue homing chemokines CXCL12, CXCL13, and beneath stromal cells. PRT318 and P505-15 inhibit Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

PRT318 completely inhibits HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Pretreatment of mice with PRT318 markedly reduces HIT IC-induced thrombosis in the lungs. The Thrombosis Score is significantly lower for PRT318-treated mice compared with control.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

PRT318 completely inhibits HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Pretreatment of mice with PRT318 markedly reduces HIT IC-induced thrombosis in the lungs. The Thrombosis Score is significantly lower for PRT318-treated mice compared with control.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Reilly MP, et al. PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model. Blood. 2011 Feb 17;117(7):2241-6.  [Content Brief]

  . Hoellenriegel J, et al. Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic lymphocytic leukemia B-cell activation and migration. Leukemia. 2012 Jul;26(7):1576-83.  [Content Brief]