(S)-Crizotinib is a selective inhibitor of the human mutT homologue MTH1 (also known as NUDT1; IC50 value 72 nM; Kd value 48 nM). MTH1 inhibition by (S)-Crizotinib induced an increase in DNA single-strand breaks, activated DNA repair in human colon carcinoma cells, and effectively suppressed tumor growth in animal models.
It is the opposite (S)-enantiomer of (R)-Crizotinib (PF-02341066, Axon 1660), which is a ALK/MET inhibitor. MTH1 (human mutT homologue, or NUDT1) has been implicated in aiding RAS-transformed cells to overcome oncogene-induced senescence by preventing reactive oxygen species (ROS)-induced DNA damage.