Discovery of novel dihydropteridone derivatives as orally bioavailable PLK1 inhibitors with reduced hERG inhibitory activity for acute myeloid leukemia treatment.

Polo like kinase 1 (PLK1) is a serine/threonine kinase that plays an important role in multiple phases of the cell cycle, inhibiting its activity has been considered an effective treatment for acute myeloid leukemia (AML). Here, we reported a series of highly potent PLK1 inhibitors. Among them, compound WD6 was identified as the most promising PLK1 inhibitor, with an IC value of 0.