WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202222
CAS#: 877399-52-5 (free base)
Description: Crizotinib, also known as PF-02341066, is an orally bioavailable agent belonging to the class of c-met/hepatocyte growth factor receptor (HGFR) tyrosine kinase inhibitors with potential antineoplastic activity. Crizotinib was approved for treatment of some non-small cell lung carcinoma (NSCLC) in the US, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and childre. Crizotinib inhibits the membrane receptor MET and activation of the MET signaling pathway, which may block tumor cell growth, migration and invasion, and tumor angiogenesis in susceptible tumor cell populations. Crizotinib was approved in 2011.
MedKoo Cat#: 202222
CAS#: 877399-52-5 (free base)
Chemical Formula: C21H22Cl2FN5O
Exact Mass: 449.11854
Molecular Weight: 450.34
Elemental Analysis: C, 56.01; H, 4.92; Cl, 15.74; F, 4.22; N, 15.55; O, 3.55
Synonym: PF02341066; PF-02341066; PF 02341066; PF2341066; PF-2341066; PF 2341066; Crizotinib; US brand name: Xalkori;
IUPAC/Chemical Name: (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine
InChi Key: KTEIFNKAUNYNJU-GFCCVEGCSA-N
InChi Code: InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m1/s1
SMILES Code: NC1=NC=C(C2=CN(C3CCNCC3)N=C2)C=C1O[C@@H](C4=C(Cl)C=CC(F)=C4Cl)C
Appearance: white to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|DMF:PBS (pH 7.2) (1:1)||0.5||1.11|
The following data is based on the product molecular weight 450.34 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Theilen TM, Soerensen J, Bochennek K, Becker M, Schwabe D, Rolle U, Klingebiel T, Lehrnbecher T. Crizotinib in ALK(+) inflammatory myofibroblastic tumors-Current experience and future perspectives. Pediatr Blood Cancer. 2017 Dec 29. doi: 10.1002/pbc.26920. [Epub ahead of print] Review. PubMed PMID: 29286567.
2: Sgambato A, Casaluce F, Maione P, Gridelli C. Targeted therapies in non-small cell lung cancer: a focus on ALK/ROS1 tyrosine kinase inhibitors. Expert Rev Anticancer Ther. 2018 Jan;18(1):71-80. doi: 10.1080/14737140.2018.1412260. Epub 2017 Dec 6. Review. PubMed PMID: 29187012.
3: Manicone M, Scaini MC, Rodriquenz MG, Facchinetti A, Tartarone A, Aieta M, Zamarchi R, Rossi E. Liquid biopsy for monitoring anaplastic lymphoma kinase inhibitors in non-small cell lung cancer: two cases compared. J Thorac Dis. 2017 Oct;9(Suppl 13):S1391-S1396. doi: 10.21037/jtd.2017.08.151. Review. PubMed PMID: 29184678; PubMed Central PMCID: PMC5676101.
4: Pellegrino B, Facchinetti F, Bordi P, Silva M, Gnetti L, Tiseo M. Lung Toxicity in Non-Small-Cell Lung Cancer Patients Exposed to ALK Inhibitors: Report of a Peculiar Case and Systematic Review of the Literature. Clin Lung Cancer. 2017 Oct 28. pii: S1525-7304(17)30302-9. doi: 10.1016/j.cllc.2017.10.008. [Epub ahead of print] Review. PubMed PMID: 29174221.
5: Institute for Quality and Efficiency in Health Care. Ceritinib -- Benefit Assessment According to §35a Social Code Book V [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2015 Sep 29. Available from http://www.ncbi.nlm.nih.gov/books/NBK458396/ PubMed PMID: 29144697.
6: Institute for Quality and Efficiency in Health Care. Crizotinib (New Therapeutic Indication) -- Benefit Assessment According to §35a Social Code Book V [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2016 Mar 30. Available from http://www.ncbi.nlm.nih.gov/books/NBK458423/ PubMed PMID: 29144683.
7: Alshareef A. Novel Molecular Challenges in Targeting Anaplastic Lymphoma Kinase in ALK-Expressing Human Cancers. Cancers (Basel). 2017 Oct 28;9(11). pii: E148. doi: 10.3390/cancers9110148. Review. PubMed PMID: 29143801; PubMed Central PMCID: PMC5704166.
8: Passaro A, Prelaj A, Pochesci A, Spitaleri G, Rossi G, Del Signore E, Catania C, de Marinis F. Brigatinib for the treatment of ALK-positive advanced non-small cell lung cancer patients. Drugs Today (Barc). 2017 Aug;53(8):435-446. doi: 10.1358/dot.2017.53.8.2676119. Review. PubMed PMID: 29119148.
9: Jain RK, Chen H. Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib. Lung Cancer (Auckl). 2017 Oct 13;8:169-177. doi: 10.2147/LCTT.S126507. eCollection 2017. Review. PubMed PMID: 29075144; PubMed Central PMCID: PMC5648304.
10: Mo HN, Liu P. Targeting MET in cancer therapy. Chronic Dis Transl Med. 2017 Jul 19;3(3):148-153. doi: 10.1016/j.cdtm.2017.06.002. eCollection 2017 Sep. Review. PubMed PMID: 29063069; PubMed Central PMCID: PMC5643781.
11: Boromand N, Hasanzadeh M, ShahidSales S, Farazestanian M, Gharib M, Fiuji H, Behboodi N, Ghobadi N, Hassanian SM, Ferns GA, Avan A. Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer. J Cell Physiol. 2017 Oct 23. doi: 10.1002/jcp.26232. [Epub ahead of print] Review. PubMed PMID: 29058790.
12: Muller IB, de Langen AJ, Giovannetti E, Peters GJ. Anaplastic lymphoma kinase inhibition in metastatic non-small cell lung cancer: clinical impact of alectinib. Onco Targets Ther. 2017 Sep 13;10:4535-4541. doi: 10.2147/OTT.S109493. eCollection 2017. Review. PubMed PMID: 28979145; PubMed Central PMCID: PMC5602476.
13: Pal P, Khan Z. ROS1-1. J Clin Pathol. 2017 Dec;70(12):1001-1009. doi: 10.1136/jclinpath-2016-204244. Epub 2017 Sep 13. Review. PubMed PMID: 28903995.
14: Cao S, Nambudiri VE. Anaplastic Lymphoma Kinase in Cutaneous Malignancies. Cancers (Basel). 2017 Sep 12;9(9). pii: E123. doi: 10.3390/cancers9090123. Review. PubMed PMID: 28895885; PubMed Central PMCID: PMC5615338.
15: Califano R, Greystoke A, Lal R, Thompson J, Popat S. Management of ceritinib therapy and adverse events in patients with ALK-rearranged non-small cell lung cancer. Lung Cancer. 2017 Sep;111:51-58. doi: 10.1016/j.lungcan.2017.06.004. Epub 2017 Jun 9. Review. PubMed PMID: 28838397.
16: Lin JJ, Shaw AT. Recent Advances in Targeting ROS1 in Lung Cancer. J Thorac Oncol. 2017 Nov;12(11):1611-1625. doi: 10.1016/j.jtho.2017.08.002. Epub 2017 Aug 14. Review. PubMed PMID: 28818606; PubMed Central PMCID: PMC5659942.
17: Santarpia M, Daffinà MG, D'Aveni A, Marabello G, Liguori A, Giovannetti E, Karachaliou N, Gonzalez Cao M, Rosell R, Altavilla G. Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and place in therapy. Drug Des Devel Ther. 2017 Jul 5;11:2047-2063. doi: 10.2147/DDDT.S113500. eCollection 2017. Review. PubMed PMID: 28740365; PubMed Central PMCID: PMC5503498.
18: Losanno T, Gridelli C. Recent advances in targeted advanced lung cancer therapy in the elderly. Expert Rev Anticancer Ther. 2017 Sep;17(9):787-797. doi: 10.1080/14737140.2017.1348232. Epub 2017 Jul 4. Review. PubMed PMID: 28656792.
19: Institute for Quality and Efficiency in Health Care. Addendum to Commission A12-15 (Crizotinib) [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2013 Apr 15. Available from http://www.ncbi.nlm.nih.gov/books/NBK385688/ PubMed PMID: 28609038.
20: Institute for Quality and Efficiency in Health Care. Crizotinib -- Benefit Assessment According to §35a Social Code Book V [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2013 Feb 13. Available from http://www.ncbi.nlm.nih.gov/books/NBK385642/ PubMed PMID: 28609030.
1. Crizotinib's phyisical and chemical properties: Crizotinib is a white to pale-yellow powder with a pKa of 9.4 (piperidinium cation) and 5.6 (pyridinium cation). 2 . The solubility of crizotinib: The solubility of crizotinib in aqueous media decreases over the range pH 1.6 to pH 8.2 from greater than 10 mg/mL to less than 0.1 mg/mL. The log of the distribution coefficient (octanol/water) at pH 7.4 is 1.65.
Crizotinib was approved for treatment of some non-small cell lung carcinoma (NSCLC) in the US and some other countries, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and children