Poloppin is a cell penetrant and potent inhibitor of mitotic Polo-like kinases (PLKs) that binds to the Polo-box domain (PBD) and prevents PLKs interaction with pSer/pThr phosphopeptide substrates. Poloppin induces mitotic arrest and apoptosis in cancer cells expressing mutant KRAS in 2D and organoid cultures. It also sensitizes mutant KRAS-expressing cancer cells to Crizotinib.