LY2784544 is a JAK2 inhibitor. LY2784544 may be used as a potential treatment for patients with myeloproliferative neoplasm.
ChEBI: Gandotinib is a member of pyridazines.
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.
Gandotinib (LY2784544) effectively inhibits STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP (green fluorescent protein) ascitic tumor cells (TED50=12.7 mg/kg) and significantly reduces (P<0.05) Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model (TED50=13.7 mg/kg, twice daily)[1].
JAK2: 3 nM (IC50); Tyk2: 44 nM (IC50); JAK3: 48 nM (IC50); FGFR2: 32 nM (IC50); FGFR3: 106 nM (IC50); Flt-4: 25 nM (IC50); KDR: 109 nM (IC50); FLT3: 4 nM (IC50); TRKB: 95 nM (IC50); ALK: 138 nM (IC50); MUSK: 147 nM (IC50); AURKA: 168 nM (IC50); MAP3K9: 299 nM (IC50)
