Licensed by Pfizer Catalog No.S1068
Molecular Weight(MW): 450.34
Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively.
Cited by 73 Publications
13 Customer Reviews
(c) Western blot analyses of p-Akt (Ser473) and p-S6RP (Ser235 and Ser236) in two RCT-E565 transplanted tumors treated with vehicle or PF02341066. Samples were isolated 4 h after the last dose from mice treated with PF02341066 for 3 d. (d) Responses of RCT-E565 transplanted tumors in athymic mice to PF02341066 or vehicle. Data are means ±s.e.m. (each group, n = 6). *P < 0.005, **P < 0.001 (Student,s t test).
Nat Med 2011 17, 1116-1120. Crizotinib (PF-02341066) purchased from Selleck.
Ba/F3 cells grown in the presence of IL-3, or Ba/F3 cells expressing native EML4-ALK (clone #2, #10, #101, and #155) and EML4-ALK L1196M (clone #216, #302, #303, and #355), were treated with CH5424802 or PF-02341066 for 48 hr, and then the viable cells were measured by the Cell Titer-Glo Luminescent Cell Viability Assay. IC50 values were determined by plotting the drug concentration versus percentage of cell growth inhibition. Data are shown as mean ±SD (n = 3).
Cancer Cell 2011 19, 679–690. Crizotinib (PF-02341066) purchased from Selleck.
Mice bearing Ba/F3-EML4-ALK (clone #10) and EML4-ALK L1196M (clone #303) were administered vehicle, CH5424802 (60 mg/kg), or PF-02341066 (100 mg/kg) orally once daily for 8 days. Tumor volume for each dose group was measured. Data are shown as mean ± SD (n = 5). Parametric Dunnett’s test: ***p < 0.001; N.S., not significant, versus vehicle treatment at final day. For pharmacodynamic assay, mice bearing Ba/F3-EML4-ALK (clone #10) and -EML4-ALK L1196M (clone #303) were orally administered at single dose of vehicle, CH5424802 (60 mg/kg), or PF-02341066 (100 mg/kg), and the tumors were collected and lysed at 4 hr post-dosing. STAT3 and phosphorylated STAT3 (Tyr 705) were detected by immunoblot analysis using antibodies against each of them (n = 2 per group).
Cancer Cell 2011 19, 679–690. Crizotinib (PF-02341066) purchased from Selleck.
Three MET amplified (Hs746t, SNU-5 and MKN45) and two non-amplified cell lines (MKN74 and NUGC-4) were incubated with or without 100nM crizotinib 24 hours, and total protein was extracted using RIPA lysis buffer. Total lysates were then analyzed by immunoblotting using anti-phospho-MET, anti-total-MET, and β-actin antibodies.
Oncotarget, 2017, 8(31):51675-51687. Crizotinib (PF-02341066) purchased from Selleck.
Viability of Ba/F3 cells stably expressing DCTN1-ALK or EML4-ALK cDNAs after treatment with crizotinib (C). Ba/F3 cells transduced with lentiviral cDNA or empty vector were subjected to the assay, and the number of cells was counted at 72 hours.
Oncologist, 2017, 22(2):158-164. Crizotinib (PF-02341066) purchased from Selleck.
Combination of EGCG with c-MET inhibitor has enhanced inhibitory effects on the growth of OS cells. MG-63 and U-2OS cells were treated with crizotinib (0.05 mM) and/or EGCG (0.08 g/L) for 48 h, and the effects on cell apoptosis (b) were determined using flow cytometry. *P<0.05 versus the control; #P<0.05 versus crizotinib-treated groups or EGCG-treated groups
Tumour Biol, 2016, 37(4):4373-82. Crizotinib (PF-02341066) purchased from Selleck.
(A) VimPro-Fluc activity in spheroids after 72-h treatment with control modulators of epithelial-mesenchymal transition (EMT) normalized to spheroid viability and compared to vimentin protein expression using Western blot analysis. (B) Dose-response curves for both U0126 and axitinib control modulators of EMT. RLU, relative luminescence units.
J Biomol Screen 2011 16, 141-154. Crizotinib (PF-02341066) purchased from Selleck.
Secondary assay development. The invasive potential of MDA-MB-231 spheroids was measured using modified Boyden chambers coated with Matrigel™. Invading cells were fixed, stained with DAPI, and quantified by fluorescence microscopy using 5 random fields per filter insert in triplicate. U0126, PF2341066, axitinib, and PKC412 inhibited the invasive potential of MDA-MB-231 spheroids by ~90% as compared to untreated spheroids (UT). ***p ≤ 0.001. IGF1R and dasatinib displayed no statistical difference as compared to UT MDA-MB-231 spheroids.
J Biomol Screen 2011 16, 141-154. Crizotinib (PF-02341066) purchased from Selleck.
Crizotinib impaired tumor vascularization. a-e Representative photomicrographs (40×) of CD31 staining in negative control and indicated LFD, HFD, vehicle (veh) and crizotinib (criz) treated groups. b CD31 was quantified on 5–6 randomly selected regions of n = 2 sections each from each mouse. N = 9–10 mice (a vs b, Veh vs Criz, P = 0.0138)
Springerplus, 2016, 5:348. Crizotinib (PF-02341066) purchased from Selleck.
Inhibition of signaling pathway activation in lung tumor cell lines by kinase inhibitors. Lung tumor cells were cultured in 10% FBS until reaching ∼80% confluence and then the cells were starved in serum-free medium for overnight, followed by 4-hour treatment with the inhibitors. Cell lysates were then prepared and used for determination of the pathway activation signals by the CEER assay.
Int J Proteomics 2011 2011, 215496. Crizotinib (PF-02341066) purchased from Selleck.
Inhibition of anchorage-independent growth of lung tumor cell lines by selected inhibitors. Each selected cell line was treated with the indicated inhibitor at 0.1 μM and 1 μM concentrations for two weeks and cell colony size formation was scored under the Nikon inverted-phase microscope.
Int J Proteomics 2011 2011, Article ID 215496. Crizotinib (PF-02341066) purchased from Selleck.
Purity & Quality Control
Choose Selective c-Met Inhibitors
|Description||Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively.|
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. PF-2341066 is >1,000-fold selective for the VEGFR2 and PDGFRβ RTKs, >250-fold selective for IRK and Lck, and ∼40- to 60-fold selective for Tie2, TrkA, and TrkB, all compared with c-Met. PF-2341066 is 20- to 30-fold selective for RON and Axl RTKs. In contrast, PF-2341066 shows a near-equivalent IC50 of 24 nM against the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) oncogenic fusion variant of the ALK RTK expressed by the KARPAS299 human anaplastic large cell lymphoma (ALCL) cell line. PF-2341066 inhibits c-Met–dependent neoplastic phenotypes of cancer cells and angiogenic phenotypes of endothelial cells. PF-2341066 suppresses human GTL-16 gastric carcinoma cell growth with IC50 of 9.7 nM. PF-2341066 induces apoptosis in GTL-16 cells with IC50 of 8.4 nM. PF-2341066 inhibits HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion with IC50 of 11 nM and 6.1 nM, respectively. PF-2341066 inhibits MDCK cell scattering with IC50 of 16 nM. PF-2341066 prevents HGF-stimulated c-Met phosphorylation, cell survival, and Matrigel invasion with IC50 of 11 nM, 14 nM and 35 nM, respectively. In addition, PF-2341066 prevents serum-stimulated HMVEC branching tubulogenesis (formation of vascular tubes) in fibrin gels.  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.  Besides, PF-2341066 prevents osteosarcoma behavior associated with primary tumor growth (i.e., proliferation and survival) as well as metastasis (eg, invasion and clonogenicity). 
|In vivo||In the GTL-16 model, 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 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. In the NCI-H441 NSCLC model, a 43% decrease in mean tumor volume is observed at 50 mg/kg/day during the 38-day PF-2341066 administration cycle. In the Caki-1 RCC model, a 53% decrease in mean tumor volume is observed to be associated with decreased volume of each tumor by at least 30% at 50 mg/kg/day during the 33-day PF-2341066 administration cycle. PF-2341066 also reveals near-complete prevention of the growth of established tumors at 50 mg/kg/day in the U87MG glioblastoma or PC-3 prostate carcinoma xenograft models, with 97% or 84% inhibition on the final study day, respectively. In contrast, PF-2341066 p.o. given at 50 mg/kg/day does not significantly inhibit tumor growth in the MDA-MB-231 breast carcinoma model, or the DLD-1 colon carcinoma model. 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. P.o. administration of PF-2341066 to severe combined immunodeficient-Beige mice bearing Karpas299 ALCL tumor xenografts leads to dose-dependent antitumor efficacy with complete regression of all tumors at the 100 mg/kg/d dose within 15 days of initial compound administration. In addition, inhibition of key NPM-ALK signaling mediators, including phospholipase C-gamma, signal transducers and activators of transcription 3, extracellular signal-regulated kinases, and Akt by PF-2341066 are observed at concentrations or dose levels, which correlated with inhibition of NPM-ALK phosphorylation and function. PF-2341066 prevents osteosarcoma behavior associated with primary tumor growth (eg, proliferation and survival) as well as metastasis (eg, invasion and clonogenicity). 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. 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.|
Cellular kinase phosphorylation ELISA assays: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.
-  Zou HY, et al. Cancer Res. 2007, 67(9), 4408-4417.
-  Christensen JG, et al. Mol Cancer Ther. 2007, 6(12 Pt 1), 3314-3322.
-  Sampson ER, et al. J Bone Miner Res. 2011, 26(6), 1283-1294.
|In vitro||DMSO||9 mg/mL (19.98 mM)|
|In vivo||Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+30% PEG 300+dd H2O
For best results, use promptly after mixing.
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT03126916||Recruiting||Childhood Ganglioneuroblastoma|Childhood Neuroblastoma|INRG Stage L2|INRG Stage M|INRG Stage MS|NMYC Gene Amplification|Recurrent Neuroblastoma||Children''s Oncology Group|National Cancer Institute (NCI)||May 9 2018||Phase 3|
|NCT01979536||Recruiting||Anaplastic Large Cell Lymphoma ALK-Positive|Ann Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell Lymphoma|Ann Arbor Stage III Noncutaneous Childhood Anaplastic Large Cell Lymphoma|Ann Arbor Stage IV Noncutaneous Childhood Anaplastic Large Cell Lymphoma|CD30-Positive Neoplastic Cells Present||National Cancer Institute (NCI)||November 8 2013||Phase 2|
|NCT02040870||Completed||Non-Small Cell Lung Cancer||Novartis Pharmaceuticals|Novartis||March 7 2014||Phase 1|Phase 2|
|NCT01531361||Active not recruiting||Advanced Malignant Neoplasm|BRAF Gene Mutation|Metastatic Malignant Neoplasm|Recurrent Malignant Neoplasm|Refractory Malignant Neoplasm||M.D. Anderson Cancer Center|National Cancer Institute (NCI)||February 6 2012||Phase 1|
|NCT02761057||Recruiting||Stage III Renal Cell Cancer AJCC v7|Stage IV Renal Cell Cancer AJCC v7|Type 1 Papillary Renal Cell Carcinoma|Type 2 Papillary Renal Cell Carcinoma||National Cancer Institute (NCI)||April 5 2016||Phase 2|
|NCT02094573||Active not recruiting||Carcinoma Non-Small-Cell Lung||Ariad Pharmaceuticals||June 4 2014||Phase 2|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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Frequently Asked Questions
Could you tell me whether this product represents the pure R-form of crizotinib, or is the the racemic Crizotinib, so a mixture of the S- and the R-form?
Our S1068 Crizotinib is R enantiomer(except batch 05 and 06, they are racemate), and S7505 is S enantiomer.