Biochem/physiol Actions

LY2784544 is an orally active, ATP-competitive, potent and JAK2-selective janus tyrosine kinase inhibitor (IC50/[ATP] = 2.52 nM/5 µM/JAK2, 19.8 nM/20 µM/JAK1, 48.0 nM/2 µM/JAK3) with little activity toward 79 other kinases. LY2784544 selectively inhibits signaling/proliferation driven by oncogenic JAK2V617F (IC50 = 20/55 nM) over those mediated by wt JAK2 upon IL-3 induction (IC50 = 1183/1309 nM) in Ba/F3 cultures and displays in vivo efficacious in a JAK2V617F-induced murine MPN model (10-80 mg/kg bid po.). LY2784544 is also reported to display Zn-dependent (optimal [Zn⁺²] = 100 µM) GPR39 agonist activity, but not 11 other GPRs.