Crizotinib-d8

Crizotinib-d8 (PF-02341066-d8) is deuterium labeled Crizotinib. Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive ALK and c-Met inhibitor with IC50s of 20 and 8 nM, respectively. Crizotinib inhibits tyrosine phosphorylation of NPM-ALK and tyrosine phosphorylation of c-Met with IC50s of 24 and 11 nM in cell-based assays, respectively. Crizotinib is also a ROS1 inhibitor. Crizotinib has effective tumor growth inhibition[1][2][3].

Product Specifications

CAS Number

[1523579-82-9]

Product Name Alternative

PF-02341066-d8

UNSPSC

12352005

Target

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

Related Pathways

Autophagy; Others; Protein Tyrosine Kinase/RTK

Applications

Cancer-Kinase/protease

Field of Research

Cancer

Smiles

C[C@H](C1=C(C(F)=CC=C1Cl)Cl)OC2=CC(C3=CN(C4C([2H])([2H])C([2H])([2H])NC([2H])([2H])C4([2H])[2H])N=C3)=CN=C2N

Molecular Formula

C21H14D8Cl2FN5O

Molecular Weight

458.39

References & Citations

[1]Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53 (2) :211-216.|[2]Liu H, et al. Identifying and Targeting Sporadic Oncogenic GeneticLiu H, et al. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple Negative Breast Cancer. Cancer Discov. 2018 Mar;8 (3) :354-369.|[3]Shen A, et al. c-Myc alterations confer therapeutic response and acquired resistance to c-Met inhibitors in MET-addicted cancers. Cancer Res. 2015 Nov 1;75 (21) :4548-59.|[4]Umapathy G, et al. The kinase ALK stimulates the kinase ERK5 to promote the expression of the oncogene MYCN in neuroblastoma. Sci Signal. 2014 Oct 28;7 (349) :ra102.|[5]Tucker ER, et al. Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma. Mol Oncol. 2017 Aug;11 (8) :996-1006.|[6]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.|[7]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|[8]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.|[9]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.