Crizotinib, Free Base (PF-02341066, PF-1066, PF-2341066, Xalkori, CAS 877399-52-5), >99%

LC Laboratories' Product Number C-7900 - Crizotinib, Free Base (PF-02341066, PF-1066, PF-2341066, Xalkori, CAS 877399-52-5), >99% - for research use only. Crizotinib, also known as PF-02341066, is a potent ATP-competitive, recombinant human c-Met kinase inhibitor (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte growth factor (HGF)-stimulated or constitutive total tyrosine phosphorylation of wild-type c-Met in a panel of human tumor and endothelial cell lines. It showed activity against c-Met phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC50 = 9.7 nM), induced apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC50s of 11 and 6.1 nM, respectively), and inhibited MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) in human umbilical vascular endothelial cells. In addition, it inhibited serum-stimulated human dermal microvascular endothelial cell branching tubulogenesis (formation of vascular tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo in c-Met-dependent human xenograft models including GTL-16 human gastric carcinoma, U87MG human glioblastoma, NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation in athymic mice bearing GTL16 tumors corresponded to the EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation (>90%) is required to significantly inhibit tumor growth (>50%). Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. 76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate was 64% and the disease control rate was 90%. Gastrointestinal toxicities (nausea and vomiting) were the most frequent adverse events. Crizotinib is the active ingredient in the drug sold under the trade name Xalkori®. This drug is currently approved in at least one country for use in patients with certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: The Crizotinib, Free Base research compound sold by LC Laboratories is NOT Xalkori®, and is NOT for human use. This crizotinib product is the free base, whose CAS number is given above.. The CAS number of the acetate salt is 877399-53-6. Another CAS number previously assigned to crizotinib, namely 912279-98-2, has been deleted by CAS and is no longer in use.

• Supplier: LC Laboratories
• Product #: C-7900
• Sku #: C-7900_5g