Researchers from Fudan University and affiliated organizations presented the discovery of novel PIM kinase inhibitors for the treatment of acute myeloid leukemia (AML). A literature-aided molecular hybridization strategy was applied to synthesize a structurally novel compound, based on an N-pyridinyl amide scaffold. Subsequent optimization showed that the positional isomerization of pyridine N toward to Lys67 resulted in a decrease of potency while increased freedom of solvent fragment toward Asp128/Glu171 led to an increase in activity.