(S)-Crizotinib is a potent inhibitor of 7,8-dihydro-8-oxoguanine triphosphatase MTH1 (NUDT1) with IC50 of 72 nM and ITC KD of 47 nM. (S)-Crizotinib has IC50 of 330 nM and 408 nM for MTH1 substrates 8-oxo-dGTP and 2-OH-dATP, respectively. (S)-Crizotinib efficiently inhibits colony formation of SW480 and KRAS mutated PANC1 cells, similar to SCH51344. (S)-Crizotinib efficiently stabilized MTH1 validating the differential targeting within cells. (S)-Crizotinib induced DNA damage in cancer cells and reduced tumour growth in SW480 colon carcinoma xenograft model.
