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(R)-CrizotinibC-MET/ALK inhibitor,potent and ATP-competitve

(R)-Crizotinib

Catalog No. A3020
Size Price Stock Qty
10mM (in 1mL DMSO) $75.00 In stock
10mg $50.00 In stock
50mg $100.00 In stock
100mg $140.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

(R)-Crizotinib

Related Biological Data

(R)-Crizotinib

Biological Activity

Description Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM, respectivley.
Targets c-Met ALK        
IC50 11 nM 24 nM        

Protocol

Cell experiment [1]:

Cell lines

LLC SP and MP cell lines

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reacting condition

12 h; IC50=21.3 nM (MP cells); cell survival rate of 50.0±0.6%=22.4 nM (SP cells)

Applications

The inhibitory effects of crizotinib on MP cells and SP cells were determined by colony formation assay. The IC50 value of crizotinib for MP cells was 21.3 nM. Of note, the SP cells showed no significant changes after crizotinib treatment. However, the SP cells showed a cell survival rate of 50.0±0.6% following a combined treatment of crizotinib (22.4 nM) and verapamil (500 µM), compared with 105.3±0.4% survival of SP cells treated with crizotinib (22.4 nM) alone. The growth curves obtained demonstrate that crizotinib inhibited the growth of SP and MP cells, and this inhibition was dependent on both concentration and time.

Animal experiment [1]:

Animal models

NU/NU nude mice

Dosage form

intratumoral injection

Application

Tumorigenicity was examined using immune-deficient mice, into which SP or MP cells of LLC were subcutaneously transplanted. Nonsorted LLC cells formed xenografts in mice at 1x105 cells. Tumor size was significantly decreased in the crizotinib-treated LLC groups (225±29 mm3) compared to the untreated group (PBS: 834±41 mm3) by 40 days after treatment.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Xia P, Gou W F, Zhao S, et al. Crizotinib may be used in lewis lung carcinoma: A novel use for crizotinib[J]. Oncology reports, 2013, 30(1): 139-148.

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Chemical Properties

Cas No. 877399-52-5 SDF Download SDF
Synonyms Crizotinib,PF-2341066, PF02341066, PF 2341066
Chemical Name 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine
Canonical SMILES CC(C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N
Formula C21H22Cl2FN5O M.Wt 450.34
Solubility Limited solubility Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Research Update

1. Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar. Int J Cancer. 2014 Mar 15;134(6):1484-94. doi: 10.1002/ijc.28475. Epub 2013 Oct 3.
Abstract
Crizotinib concentrations in plasma and brain are regulated by Abcb1 only if a non-saturating dose is applied. The co-administration of elacridar and crizotinib not only substantially increases crizotinib concentrations in plasma and brain but also promotes the delivery of crizotinib to the brain.
2. Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC. Ann Oncol. 2014 Feb;25(2):415-22. doi: 10.1093/annonc/mdt572.
Abstract
Crizotinib, a drug approved for the treatment of ALK-positive NSCLC, has been investigated for its clinical benefits in crizotinib-treated patients who have developed PD.
4. Crizotinib may be used in Lewis lung carcinoma: a novel use for crizotinib. Oncol Rep. 2013 Jul;30(1):139-48. doi: 10.3892/or.2013.2424. Epub 2013 Apr 24.
Abstract
Crizotinib is an inhibitor of ALK that has been approved by FDA for the treatment of locally advanced or metastatic ALK-positive NSCLC. Crizotinib also exhibited antitumor activity in LLC cell lines, where it induced apoptosis and G1 phase arrest in LLC MP cells; inhibited cell proliferation in LLC SP cells; suppressed tumor growth and angiogenesis in established xenografted tumors; and activated the Smad signaling pathway.

Background

Crizotinib is a potent, ATP-competitive, small-molecule and orally available inhibitor of c-Met kinase with a Ki value of 4 nmol/L[1].

Crizotinib has shown to inhibit wild-type c-Met phosphorylation with a mean IC50 value of 11 nmol/L in multiple human endothelial and carcinoma cell lines. Crizotinib has been demonstrated to inhibit cell growth and induce apoptosis in human GTL-16 gastric carcinoma cells. Additionally, crizotinib could inhibit cell migration and invasion induced by HGF in human NCI-H441 lung cancer cells. Moreover, crizotinib has revealed to block cell scattering of MDCK [1].

Crizotinib has been indicated to suppress tumor growth in GTL-16, NCI-H441 NSCLC, Caki-1 RCC, U87MG glioblastoma or PC-3 prostate tumor xenograft mice [1].

References:
[1] Zou HY1, Li Q, Lee JH, Arango ME, McDonnell SR, Yamazaki S, Koudriakova TB, Alton G, Cui JJ, Kung PP, Nambu MD, Los G, Bender SL,Mroczkowski B, Christensen JG. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007 May 1;67(9):4408-17.