Home Tools
Log in
Cart

Crizotinib

Catalog No. T1661   CAS 877399-52-5
Synonyms: PF-02341066

Crizotinib (PF-02341066) is an ATP-competitive small-molecule tyrosine kinases inhibitor of c-MET (IC50: 8 nM) and ALK (IC50: 20 nM) receptor.

All products from TargetMol are for Research Use Only. Not for Human or Veterinary or Therapeutic Use.
Crizotinib Chemical Structure
Crizotinib, CAS 877399-52-5
Pack Size Availability Price/USD Quantity
10 mg In stock $ 46.00
25 mg In stock $ 55.00
50 mg In stock $ 63.00
100 mg In stock $ 85.00
200 mg In stock $ 98.00
500 mg In stock $ 158.00
1 mL * 10 mM (in DMSO) In stock $ 48.00
Bulk Inquiry
Get quote
Select Batch  
Purity: 99.87%
Purity: 99.35%
Purity: 99%
Contact us for more batch information
Biological Description
Chemical Properties
Storage & Solubility Information
Description Crizotinib (PF-02341066) is an ATP-competitive small-molecule tyrosine kinases inhibitor of c-MET (IC50: 8 nM) and ALK (IC50: 20 nM) receptor.
Targets&IC50 ALK:24 nM (cell free), c-Met:11 nM (A498 cells)
In vitro Crizotinib (PF-2341066) potently inhibited c-Met phosphorylation and c-Met-dependent proliferation, migration, or invasion of human tumor cells in vitro (IC50: 5-20 nmol/L). In addition, PF-2341066 potently inhibited HGF-stimulated endothelial cell survival or invasion and serum-stimulated tubulogenesis in vitro [1]. Both of two cell lines with MET amplification, EBC-1, and H1993, were sensitive to crizotinib (IC50: 10 nM). In contrast, crizotinib did not substantially inhibit the proliferation of lung cancer cells with a MET mutation (H2122, H1437, and H596) [2]. PF-2341066 potently inhibited NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells (IC50: 24 nmol/L). PF-2341066 potently inhibited cell proliferation, which was associated with G(1)-S-phase cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells (IC50: 30 nmol/L) but not ALK-negative lymphoma cells. The induction of apoptosis was confirmed using terminal deoxyribonucleotide transferase-mediated nick-end labeling and Annexin V staining (IC50: 25-50 nmol/L) [3].
In vivo PF-2341066 showed efficacy at well-tolerated doses, including marked cytoreductive antitumor activity, in several tumor models that expressed activated c-Met. The antitumor efficacy of PF-2341066 was dose-dependent and showed a strong correlation to the inhibition of c-Met phosphorylation in vivo. Near-maximal inhibition of c-Met activity for the full dosing interval was necessary to maximize the efficacy of PF-2341066. Additional mechanism-of-action studies showed a dose-dependent inhibition of c-Met-dependent signal transduction, tumor cell proliferation (Ki67), induction of apoptosis (caspase-3), and reduction of microvessel density (CD31) [1]. Treatment of c-MET-amplified GTL-16 xenografts with 50 mg/kg crizotinib caused tumor regression that was associated with a slow reduction in (18)F-FDG uptake and reduced expression of the GLUT-1. Although baseline (18)F-FDG uptake into U87MG tumors was substantially higher than in GTL-16 tumors, (18)F-FDG uptake into U87MG tumors remained unchanged on treatment at 50 mg/kg crizotinib, despite tumor growth inhibition of 93% on day 8 of treatment [4].
Kinase Assay c-Met catalytic activity was quantitated using a continuous-coupled spectrophotometric assay in which the time-dependent production of ADP by c-Met was determined by analysis of the rate of consumption of NADH. NADH consumption was measured by a decrease in absorbance at 340 nm by spectrophotometry at designated time points. To determine Ki values, PF-2341066 was introduced into test wells at various concentrations in the presence of assay reagents and incubated for 10 min at 37°C. The assay was initiated by the addition of the c-Met enzyme [1].
Cell Research Cells were seeded in 96-well plates in media supplemented with 10% fetal bovine serum (FBS) and transferred to serum-free media (with 0.04% BSA) after 24 h. In experiments investigating ligand-dependent RTK phosphorylation, corresponding growth factors were 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 were washed once with HBSS supplemented with 1 mmol/L Na3VO4, and protein lysates were generated from cells. Subsequently, phosphorylation of selected protein kinases was 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 were (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′-tetramethylbenzidine peroxidase substrate to initiate a colorimetric reaction that was stopped by adding 0.09 N H2SO4; and (f) measured for absorbance in 450 nm using a spectrophotometer [1].
Animal Research Daily treatment with PF-2341066 given in water by oral gavage was initiated when tumors were 100 to 600 mm^3 in volume. Tumor volume was determined by measurement with electronic Vernier calipers, and tumor volume was calculated as the product of its length × width2 × 0.4. Tumor volume was expressed on indicated days as the median tumor volume ± SE indicated for groups of mice. Percent (%) inhibition values were measured on the final day of study for drug-treated compared with vehicle-treated mice and are calculated as 100 × {1?[(TreatedFinal day ? TreatedDay 1)/(ControlFinal day ? ControlDay 1)]}. Tumor regression values were determined by calculating the ratio of median tumor volumes at the time when treatment was initiated to the median tumor volume on the final day of study for a given treatment group. Significant differences between the treated versus the control groups (P ≤ 0.001) were determined using one-way ANOVA [1].
Synonyms PF-02341066
Molecular Weight 450.34
Formula C21H22Cl2FN5O
CAS No. 877399-52-5

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 10 mg/mL (22.21 mM)

2eq.HCl: 45 mg/mL (100 mM)

TargetMolReferences and Literature

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. Tanizaki J, et al. MET tyrosine kinase inhibitor crizotinib (PF-02341066) shows differential antitumor effects in non-small cell lung cancer according to MET alterations.J Thorac Oncol. 2011 Oct;6(10):1624-31. 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. 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 6. 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. 7. Yang Y, Huang J, Xie N, et al. lincROR influences the stemness and crizotinib resistance in eMl–alK+ non-small-cell lung cancer cells[J]. OncoTargets and therapy. 2018 Jun 22;11:3649-3657. 8. Hu Y, Zhang X, Zhao Z, et al. Keratinocytes apoptosis contributes to crizotinib induced-erythroderma[J]. Toxicology Letters. 2019 9. Tao J, Tu Y, Liu P, et al. Detection of colorectal cancer using a small molecular fluorescent probe targeted against c-Met[J]. Talanta. 2021: 122128.

TargetMolCitations

1. Yan H, Wu W, Hu Y, et al.Regorafenib inhibits EphA2 phosphorylation and leads to liver damage via the ERK/MDM2/p53 axis.Nature Communications.2023, 14(1): 2756. 2. Li P, Jia C, Fan Z, et al.Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with MET alterations.Acta Pharmaceutica Sinica B.2023 3. Zou X, Zeng M, Zheng Y, et al.Comparative Study of Hydroxytyrosol Acetate and Hydroxytyrosol in Activating Phase II Enzymes.Antioxidants.2023, 12(10): 1834. 4. Jiao D, Chen Y, Liu X, et al.Targeting MET endocytosis or degradation to overcome HGF-induced gefitinib resistance in EGFR-sensitive mutant lung adenocarcinoma.Biochemical and Biophysical Research Communications.2023 5. Yu J, Zhang L, Peng J, et al. Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways. Biochemical pharmacology. 2022, 195: 114864. 6. Arechederra M, Bazai S K, Abdouni A, et al. ADAMTSL5 is an epigenetically activated gene underlying tumorigenesis and drug resistance in hepatocellular carcinoma. Journal of Hepatology. 2021, 74(4): 893-906. 7. Yang Y, Huang J, Xie N, et al. lincROR influences the stemness and crizotinib resistance in eMl–alK+ non-small-cell lung cancer cells. OncoTargets and Therapy. 2018 Jun 22;11:3649-3657 8. Tao J, Tu Y, Liu P, et al. Detection of colorectal cancer using a small molecular fluorescent probe targeted against c-Met. Talanta. 2021: 122128. 9. Hu Y, Zhang X, Zhao Z, et al. Keratinocytes apoptosis contributes to crizotinib induced-erythroderma. Toxicology Letters. 2019 10. Zheng Y D, Zhong T, Wu H, et al. Crizotinib Shows Antibacterial Activity against Gram-Positive Bacteria by Reducing ATP Production and Targeting the CTP Synthase PyrG. Microbiology Spectrum. 2022: e00884-22
Hide

Related compound libraries

This product is contained In the following compound libraries:
Anti-Cancer Clinical Compound Library Tyrosine Kinase Inhibitor Library Anti-Cancer Approved Drug Library Anti-Cancer Drug Library Anti-Cancer Active Compound Library ReFRAME Related Library FDA-Approved & Pharmacopeia Drug Library Angiogenesis related Compound Library Pediatric Drug Library Bioactive Compounds Library Max

Related Products

Related compounds with same targets
AMG-458 RPI-1 Merestinib Foretinib URMC-099 PF-04217903 methanesulfonate Norcantharidin XL092

TargetMolDose Conversion

You can also refer to dose conversion for different animals. More

TargetMol In vivo Formulation Calculator (Clear solution)

Step One: Enter information below
Dosage
mg/kg
Average weight of animals
g
Dosing volume per animal
ul
Number of animals
Step Two: Enter the in vivo formulation
% DMSO
%
% Tween 80
% ddH2O
Calculate Reset

TargetMolCalculator

Molarity Calculator
Dilution Calculator
Reconstitution Calculation
Molecular Weight Calculator
=
X
X

Molarity Calculator allows you to calculate the

  • Mass of a compound required to prepare a solution of known volume and concentration
  • Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Concentration of a solution resulting from a known mass of compound in a specific volume
See Example

An example of a molarity calculation using the molarity calculator
What is the mass of compound required to make a 10 mM stock solution in 10 ml of water given that the molecular weight of the compound is 197.13 g/mol?
Enter 197.13 into the Molecular Weight (MW) box
Enter 10 into the Concentration box and select the correct unit (millimolar)
Enter 10 into the Volume box and select the correct unit (milliliter)
Press calculate
The answer of 19.713 mg appears in the Mass box

X
=
X

Calculator the dilution required to prepare a stock solution

Calculate the dilution required to prepare a stock solution
The dilution calculator is a useful tool which allows you to calculate how to dilute a stock solution of known concentration. Enter C1, C2 & V2 to calculate V1.

See Example

An example of a dilution calculation using the Tocris dilution calculator
What volume of a given 10 mM stock solution is required to make 20ml of a 50 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=50 μM, V2=20 ml and V1 is the unknown:
Enter 10 into the Concentration (start) box and select the correct unit (millimolar)
Enter 50 into the Concentration (final) box and select the correct unit (micromolar)
Enter 20 into the Volume (final) box and select the correct unit (milliliter)
Press calculate
The answer of 100 microliter (0.1 ml) appears in the Volume (start) box

=
/

Calculate the volume of solvent required to reconstitute your vial.

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial.
Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

g/mol

Enter the chemical formula of a compound to calculate its molar mass and elemental composition

Tip: Chemical formula is case sensitive: C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed n the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

bottom

Tech Support

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

Crizotinib 877399-52-5 Angiogenesis Autophagy Immunology/Inflammation Tyrosine Kinase/Adaptors c-Met/HGFR ROS ALK ROS Kinase PF-02341066 Cluster of differentiation 246 PF02341066 Inhibitor Anaplastic lymphoma kinase inhibit CD246 PF 02341066 ALK tyrosine kinase receptor Anaplastic lymphoma kinase (ALK) inhibitor

 

TargetMol