Pexmetinib is an orally bioavailable small-molecule inhibitor of p38 MAPK (β isoforms) and Tie2 kinases [2
]. It is a type 2 kinase inhibitor that binds both Tie2 and p38 MAP kinases in the "DFG-out" conformation. p38 MAPK is a proinflammatory kinase, Tie2 is an endothelial cell specific receptor tyrosine kinase and is the receptor for angiopoietin-1
. Concomitant inhibition of these kinases is predicted to produce antineoplastic, anti-inflammatory and antiangiogenic effects that would provide a novel anti-cancer therapeutic, in particular for the treatment of myelodysplastic syndromes (MDS) [1
] and acute myeloid leukemia (AML).