In vitro activity: PRT318 inhibits platelet activation via GPVI/FcRγ, an ITAM receptor complex, but not via ADP or thrombin, which are G-protein coupled receptors. PRT318 effectively antagonizes CLL(chronic lymphocytic leukemia) cell survival after BCR triggering and in nurse-like cell-co-cultures. PRT318 inhibits Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering.

Kinase Assay: PRT-060318 (also known as PRT318) is a novel, potent, selective inhibitor of the Syk tyrosine kinase, as an approach to HIT treatment. PRT-060318 was identified as a potent inhibitor of purified Syk kinase. Syk kinase was inhibited by 92%, while the activities all other kinases retained more than 70% when PRT-060318 were evaluated at a concentration of 50 nM in a broad panel of kinase enzyme assays.

Cell Assay: PRT-060318 was identified as a potent inhibitor of purified Syk kinase. Syk kinase was inhibited by 92%, while the activities all other kinases retained more than 70% when PRT-060318 were evaluated at a concentration of 50 nM in a broad panel of kinase enzyme assays. In addition, PRT-060318 could dose-responsively inhibited convulxin-induced human PRP aggregation. Moreover, it was found that PRT-060318 was able to dose-responsively inhibit the increases in intracellular calcium in convulxin-treated platelets. The numbers of cells treated with various doses of PRT318 are followed over time. PRT318 inhibits growth of the sensitive cell lines in a dose-dependent manner. Two sensitive (LY7 and LY18) and 2 resistant (LY3 and LY4) cell lines are treated with indicated doses of PRT318.