Merck (S)-Crizotinib

(S)-Crizotinib

≥98% (HPLC)

3-[(1S)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-2-pyridinamine

Quality Level

100

assay

≥98% (HPLC)

form

powder

manufacturer/tradename

Pfizer®

색상

white to beige

solubility

DMSO: 5 mg/mL, clear (warmed)

주관자

Pfizer

저장 온도

room temp

SMILES string

ClC1=C([C@H](C)OC2=C(N)N=CC(C3=CN(C4CCNCC4)N=C3)=C2)C(Cl)=C(F)C=C1

InChI

1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m0/s1

InChI key

KTEIFNKAUNYNJU-LBPRGKRZSA-N

(S)-Crizotinib has a distinctly different profile from its (R)-enantiomer, the clinically approved anticancer agent Xalkori. Instead of targeting ALK, MET and ROS1, (S)-Crizotinib is a highly selective inhibitor of human 7,8-Dihydro-8-oxoguaninetriphosphatase MTH1 (NUDT1) with an IC50 value of 330 nM, 16-fold higher affinity towards MTH1 compared to the clinically used (R)-isomer. MTH1 hydrolyzes oxidized purine nucleoside triphosphates that might otherwise be incorporated into DNA/RNA and contribute to DNA damage. MTH1 removal of oxidized nucleotides that result from increased levels of reactive oxygen species (ROS) in fast-proliferating cancer cells helps protect cancer cells from proliferative stress and prevent cancer cell death. It is considered a new target for cancer therapy. In mouse xenograft studies using SW480 cells, (S)-crizotinib but not the (R)-enantiomer, was able to impair overall tumour progression as well as specifically reduce tumour volume by more than 50%.