[CAS NO. 877399-52-5]  Crizotinib

Crizotinib (PF-02341066) displays similar potency against c-Met phosphorylation in mIMCD3 mouse or MDCK canine epithelial cells with IC ₅₀ of 5 nM and 20 nM, respectivly. PF-2341066 shows improved or similar activity against NIH3T3 cells engineered to express c-Met ATP-binding site mutants V1092I or H1094R or the P-loop mutant M1250T with IC ₅₀ of 19 nM, 2 nM and 15 nM, respectively, compared with NIH3T3 cells expressing wild-type receptor with IC ₅₀ of 13 nM. In contrast, a marked shift in potency of PF-2341066 is observed against cells engineered to express c-Met activation loop mutants Y1230C and Y1235D with IC ₅₀ of 127 nM and 92 nM, respectively, compared with wild-type receptor. PF-2341066 also potently prevents the phosphorylation of c-Met in NCI-H69 and HOP92 cells, with IC ₅₀ of 13 nM and 16 nM, respectively, which express the endogenous c-Met variants R988C and T1010I, respectively ^[1] .
Crizotinib (PF-02341066) also potently inhibits NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells with an IC ₅₀ of 24 nM. PF-2341066 potently prevents cell proliferation, which is associated with G(1)-S-phase cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells with IC ₅₀ of 30 nM, but not ALK-negative lymphoma cells ^[2] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.