LY2784544

LY2784544 is a small molecule selective mutant JAK2 kinase inhibitor with an IC50 of 68 nM. The antiproliferative activity of LY2784544 and its ability to induce apoptosis were examined by Celltiter-Glo Cell Viability and Caspase-Glo 3/7 Apoptosis Assays, respectively.? In the in vitro tests using Ba/F3 cells expressing either wild type or V617F mutant JAK2, it potently inhibited the JAK2 V617F-STAT5 signaling at a concentration that was 41-fold lower than that required to inhibit IL-3-activated wild type JAK2-STAT5 signaling (IC50 = 0.055 uM for JAK2 V617F vs. 2.26 uM for WT JAK2). Similarly in the proliferation assay, LY2784544 selectively inhibited the JAK2 V617F-driven cell proliferation (IC50= 0.068 uM). Inhibition of JAK2 V617F signaling correlated well with the induction of apoptosis (EC50= 0.113 uM) in Ba/F3 cell model.