(S)-Crizotinib

Description

MW 450.3 Da, Purity >98 %. S -crizotinib is a low nanomolar inhibitor of 7,8-dihydro-8-oxoguanine triphosphatase MTH1 or NUDT1 whereas the R -enantiomer shows IC50 values in the micromolar range. MTH1 aids in RAS-transformed cells to overcome oncogene-induced senescence by preventing reactive oxygen species ROS -induced DNA damage. The average IC50 values for S -crizotinib and the MTH1 substrates 8-oxo-dGTP and 2-OH-dATP is 330 nM and 408 nM respectively. In vitro Kd measurements indicate that S -crizotinib is considerably less potent than the R -enantiomer against the targets ALK, MET and ROS1. S -crizotinib reduces tumor volume by more than 50 % in mouse xenograft studies using SW480 cells.