Crizotinib-d9 (hydrochloride)

Crizotinib-d9 hydrochloride is deuterated labeled Crizotinib hydrochloride. Crizotinib hydrochloride (PF-02341066 hydrochloride) is an orally bioavailable, selective, and ATP-competitive dual ALK and c-Met inhibitor with IC50s of 20 and 8 nM, respectively. Crizotinib hydrochloride (PF-02341066 hydrochloride) inhibits tyrosine phosphorylation of NPM-ALK and tyrosine phosphorylation of c-Met with IC50s of 24 and 11 nM in cell-based assays, respectively. It is also a ROS proto-oncogene 1 (ROS1) inhibitor. Crizotinib hydrochloride (PF-02341066 hydrochloride) has effective tumor growth inhibition[1][2][3].

PF-02341066-d9 (hydrochloride)

12352005

Anaplastic lymphoma kinase (ALK) ; Autophagy; c-Met/HGFR; Isotope-Labeled Compounds; ROS Kinase

Isotope-Labeled Compounds

Autophagy; Others; Protein Tyrosine Kinase/RTK

Cancer-Kinase/protease

Cancer

10 mM in DMSO

NC1=C(C=C(C=N1)C2=CN(N=C2)C3(C([2H])(C([2H])([2H])NC([2H])([2H])C3([2H])[2H])[2H])[2H])O[C@H](C)C4=C(C=CC(F)=C4Cl)Cl.Cl

C21H14D9Cl3FN5O

495.85

[1]Zou HY, et al. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007, 67 (9), 4408-4417.|[2]Cullinane C, et al. Differential (18) F-FDG and 3'-deoxy-3'- (18) F-fluorothymidine PET responses to pharmacologic inhibition of the c-MET receptor in preclinical tumor models. J Nucl Med. 2011 Aug;52 (8) :1261-7|[3]Christensen JG, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther. 2007, 6 (12 Pt 1), 3314-3322.|[4]Cui JJ, et al. Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK) . J Med Chem. 2011 Sep 22;54 (18) :6342-63.|[5]Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53 (2) :211-216.

Room temperature

Isotope-Labeled Compounds