(S)-Crizotinib

1374356-45-2

450.34

DMSO : 12.5 mg/mL (27.76 mM; Need ultrasonic)

Apoptosis; Cell Cycle/DNA Damage

(S)-Crizotinib is a potent and selective MTH1 (mutT homologue) inhibitor with an IC₅₀ of 330 nM. (S)-Crizotinib disrupts nucleotide pool homeostasis via MTH1 inhibition, induces an increase in DNA single strand breaks, activates DNA repair in human colon carcinoma cells, and effectively suppresses tumour growth in animal models^[1]. IC50 & Target: IC50: 330 nM (MTH1)^[1] In Vitro: (S)-crizotinib (0.625-80 uM; 24 hours) decreases the viability of NCI-H460, H1975 and A549 cells with IC₅₀ values of 14.29, 16.54 and 11.25 uM, respectively^[2].
(S)-crizotinib (10-30 uM; 24 hours) induces NCI-H460, H1975 and A549 cells apoptosis^[2].
(S)-crizotinib (10-30 uM; 24 hours) decreases Bcl-2: Bax ratio. (S)-crizotinib decreases B cell lymphoma 2 (Bcl-2), and Bcl-2 associated protein x (Bax) is either unaltered (H460 cells) or shows an increase (H1975 cells)^[2].
(S)-Crizotinib induces apoptosis in human non-small cell lung cancer (NSCLC) cells by activating ROS-dependent ER stress apoptotic pathway independent of mutT homologue (MTH1)^[2].
In Vivo: (S)-crizotinib (7.5 or 15 mg/kg; intraperitoneal injections; once daily for 10 days) results in significant reductions in both tumor volume and tumor weight^[2].