1. Protein Tyrosine Kinase/RTK
    Autophagy
  2. c-Met/HGFR
    ALK
    Autophagy

Crizotinib (Synonyms: PF-02341066)

Cat. No.: HY-50878 Purity: 99.97% ee.: 99.63%
Handling Instructions

Crizotinib is a potent inhibitor of c-Met and ALK with an IC50 of 11 nM and 24 nM in cell-based assays, respectively.

For research use only. We do not sell to patients.

Crizotinib Chemical Structure

Crizotinib Chemical Structure

CAS No. : 877399-52-5

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 66 In-stock
Estimated Time of Arrival: December 31
10 mg USD 60 In-stock
Estimated Time of Arrival: December 31
50 mg USD 108 In-stock
Estimated Time of Arrival: December 31
100 mg USD 144 In-stock
Estimated Time of Arrival: December 31
200 mg USD 228 In-stock
Estimated Time of Arrival: December 31
500 mg USD 348 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Other Forms of Crizotinib:

    Crizotinib purchased from MCE. Usage Cited in: Cancer Discov. 2018 Mar;8(3):354-369.

    At 50mg/kg, Crizotinib inhibits MET phosphorylation and downstream signaling pathway activation.

    Crizotinib purchased from MCE. Usage Cited in: Oncotarget. 2014 May 15;5(9):2688-702.

    The Ret expression level is investigated by Western blot in MYCN/KI AlkR1279Q and MYCN/KI AlkF1178L treated tumors and controls using the anti-Ret antibody EPR2871. Actin is used as a standard for quantification.

    Crizotinib purchased from MCE. Usage Cited in: Sci Signal. 2014 Oct 28;7(349):ra102.

    Activation of ERK5 in neuroblastoma cell lines expressing activated ALK. (A to C) Immunoblotting for the indicated proteins in neuroblastoma cells CLB-BAR (A), CLB-GE (B), and IMR32 (C) cultured on six-well plates in complete growth medium and treated with inhibitors as indicated for 6 hours alone (A and B) or before (C) stimulation with mAb46 for 30 min.

    Crizotinib purchased from MCE. Usage Cited in: Oncotarget. 2016 May 17;7(20):29011-22.

    A, B. CLB-BAR (ALK-Δ4-11) and CLB-GE (ALK-F1174V), both ALK addicted cell lines, are treated with increasing doses of Brigatinib for 6 hours. Crizotinib (250 nM) is employed as a positive control. Cells lysates are resolved on SDS/PAGE followed by immunoblotting for pALK (Y1604) and additional downstream targets as indicated.

    Crizotinib purchased from MCE. Usage Cited in: Dis Model Mech. 2016 Sep 1;9(9):941-52.

    CLB-BAR, CLB-GE neuroblastoma cells are treated for 6 h with either Crizotinib or PF-04643922. Cells are harvested and pre-cleared cell lysates are analyzed on SDS PAGE followed by western blotting for ALK, phospho-ALK-Y1278, phospho-ERK5, pan-ERK5 phospho-ERK1/2 and pan-ERK. Actin is employed as a loading control. Protein band intensities are quantified by Image Studio Lite 3.1 and normalized to untreated samples.

    Crizotinib purchased from MCE. Usage Cited in: Mol Oncol. 2017 Aug;11(8):996-1006.

    Dose-response and time course comparison of ALK inhibition by Crizotinib or Ceritinib.

    Crizotinib purchased from MCE. Usage Cited in: Cancer Lett. 2018 May 28;422:19-28.

    CD74-ROS1 or CD74-ROS1 G2032R mutation cells are treated with Crizotinib for 24 h, the expression of ROS1 or p-ROS1 is determined by western blot.

    Crizotinib purchased from MCE. Usage Cited in: J Hematol Oncol. 2018 Aug 29;11(1):109.

    Resistant cells are treated with 200 nM Afatinib alone or in combination with 1 μM Crizotinib for 48 h.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Crizotinib is a potent inhibitor of c-Met and ALK with an IC50 of 11 nM and 24 nM in cell-based assays, respectively.

    IC50 & Target

    IC50: 11 nM (c-Met), 24 nM (ALK)

    In Vitro

    PF-2341066 displays similar potency against c-Met phosphorylation in mIMCD3 mouse or MDCK canine epithelial cells with IC50 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 IC50 of 19 nM, 2 nM and 15 nM, respectively, compared with NIH3T3 cells expressing wild-type receptor with IC50 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 IC50 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 IC50 of 13 nM and 16 nM, respectively, which express the endogenous c-Met variants R988C and T1010I, respectively[1]. PF-2341066 also potently inhibits NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells with an IC50 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 IC50 of 30 nM, but not ALK-negative lymphoma cells[2]. Besides, PF-2341066 prevents osteosarcoma behavior associated with primary tumor growth (i.e., proliferation and survival) as well as metastasis[3].

    In Vivo

    PF-2341066 reveals the ability to cause marked regression of large established tumors (> 600 mm3) in both the 50 mg/kg/day and 75 mg/kg/day treatment cohorts, with a 60% decrease in mean tumor volume over the 43-day administration schedule in the GTL-16 model. In an another study, PF-2341066 displays the ability to completely inhibits GTL-16 tumor growth for >3 months, with only 1 of 12 mice exhibiting a significant increase in tumor growth over the 3-month treatment schedule at 50 mg/kg/day. A significant dose-dependent reduction of CD31-positive endothelial cells is observed at 12.5 mg/kg/day, 25 mg/kg/day, and 50 mg/kg/day in GTL-16 tumors, indicating that inhibition of MVD shows a dose-dependent correlation to antitumor efficacy. PF-2341066 displays a significant dose-dependent reduction of human VEGFA and IL-8 plasma levels in both the GTL-16 and U87MG models. Marked inhibition of phosphorylated c-Met, Akt, Erk, PLCλ1, and STAT5 levels is observed in GTL-16 tumors following p.o. administration of PF-2341066[1]. PF-2341066 prevents osteosarcoma behavior associated with primary tumor growth as well as metastasis. In nude mice treated with PF-2341066 via oral gavage, the growth and associated osteolysis and extracortical bone matrix formation of osteosarcoma xenografts are prevented by PF-2341066[3]. Treatment of c-MET-amplified GTL-16 xenografts with 50 mg/kg PF-2341066 elicits tumor regression that is associated with a slow reduction in 18F-FDG uptake and decreases expression of the glucose transporter 1, GLUT-1[4].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    DMSO : 55 mg/mL (122.13 mM; Need ultrasonic)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.2205 mL 11.1027 mL 22.2054 mL
    5 mM 0.4441 mL 2.2205 mL 4.4411 mL
    10 mM 0.2221 mL 1.1103 mL 2.2205 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Crizotinib (PF-02341066) is dissolved in DMSO and sterile PBS[5].

    • 2.

      Crizotinib is formulated in 90% poly(ethylene glycol) and 10% 1-methyl-2-pyrrolidinone solution[6].

    • 3.

      Crizotinib is dissolved in sterile water with 10% Tween 20[7].

    • 4.

      Crizotinib is prepared in vehicle (0.5% methylellulose/0.5% Tween80)[8].

    References
    Kinase Assay
    [1]

    Cells are seeded in 96-well plates in media supplemented with 10% fetal bovine serum (FBS) and transferred to serum-free media [with 0.04% bovine serum albumin (BSA)] after 24 h. In experiments investigating ligand-dependent RTK phosphorylation, corresponding growth factors are added for up to 20 min. After incubation of cells with PF-2341066 for 1 h and/or appropriate ligands for the designated times, cells are washed once with HBSS supplemented with 1 mM Na3VO4, and protein lysates are generated from cells. Subsequently, phosphorylation of selected protein kinases is assessed by a sandwich ELISA method using specific capture antibodies used to coat 96-well plates and a detection antibody specific for phosphorylated tyrosine residues. Antibody-coated plates are (a) incubated in the presence of protein lysates at 4°C overnight; (b) washed seven times in 1% Tween 20 in PBS; (c) incubated in a horseradish peroxidase-conjugated anti-total-phosphotyrosine (PY-20) antibody (1:500) for 30 min; (d) washed seven times again; (e) incubated in 3,3′,5,5′-tetramethyl benzidine peroxidase substrate to initiate a colorimetric reaction that is stopped by adding 0.09 N H2SO4; and (f) measured for absorbance in 450 nm using a spectrophotometer.

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

    Cell Assay
    [1]

    Tumor cells are seeded in 96-well plates at low density in media supplemented with 10% FBS (growth media) and transferred to serum-free media (0% FBS and 0.04% BSA) after 24 h. Appropriate controls or designated concentrations of PF-2341066 are added to each well, and cells are incubated for 24 to 72 h. Human umbilical vascular endothelial cells (HUVEC) are seeded in 96-well plates in EGM2 media for 5 to 6 h at > 20,000 cells per well and transferred to serum-free media overnight. The following day, appropriate controls or designated concentrations of PF-2341066 are added to each well, and after 1 h incubation, HGF is added to designated wells at 100 ng/mL. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay is done to determine the relative tumor cell or HUVEC numbers.

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

    Animal Administration
    [1]

    Athymic mice bearing xenografts (300-800 mm3) are given PF-2341066 in water by oral gavage at designated dose levels. At designated times following PF-2341066 administration, mice are humanely euthanized, and tumors are resected. Tumors are snap frozen and pulverized using a liquid nitrogen-cooled cryomortar and pestle, protein lysates are generated, and protein concentrations are determined using a BSA assay. The level of total and phosphorylated protein is determined using a capture ELISA or immunoprecipitation-immunoblotting method.

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

    References
    Molecular Weight

    450.34

    Formula

    C₂₁H₂₂Cl₂FN₅O

    CAS No.

    877399-52-5

    SMILES

    ClC1=C(F)C=CC(Cl)=C1[[email protected]](OC2=CC(C3=CN(N=C3)C4CCNCC4)=CN=C2N)C

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.97% ee.: 99.63%

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    Product Name:
    Crizotinib
    Cat. No.:
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    Cat. No.: HY-50878