WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H202222
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.
Hodoodo Cat#: H202222
Name: Crizotinib
CAS#: 877399-52-5 (free base)
Chemical Formula: C21H22Cl2FN5O
Exact Mass: 449.12
Molecular Weight: 450.340
Elemental Analysis: C, 56.01; H, 4.92; Cl, 15.74; F, 4.22; N, 15.55; O, 3.55
Related CAS #: 877399-53-6 (acetate) 877399-52-5 (free base)
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
More Info: 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
| Biological target: | Crizotinib (PF-02341066) is an ALK and c-Met inhibitor with IC50s of 20 and 8 nM, respectively. |
| In vitro activity: | Whether crizotinib induces apoptotic cell death was tested using annexin V analysis. As seen in Figure 2D, apoptotic cell death was greatly increased after treatment with 5 μM crizotinib, compared to treatment with the control. This indicated that the reduction in the number of cells at the G2 arrest stage by crizotinib contributes to increased apoptotic death. In a detailed analysis of annexin V, it was determined whether early or late apoptotic cellular death was increased when the drug concentration increased. As seen in Figures 2D,E, crizotinib at 10 μM largely increased late apoptosis in comparison with 5 μM crizotinib, whereas early apoptosis was not increased much. This suggests that crizotinib could directly induce apoptotic cellular death, without delay, via the early apoptotic pathway. Overall, low-dose crizotinib strongly sensitized P-gp-overexpressing resistant KBV20C cells via G2 cell cycle arrest and apoptosis. Reference: Front Oncol. 2020 May 12;10:696. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247847/ |
| In vivo activity: | The antitumor action of crizotinib was examined in in vivo BALB/c nude mouse xenograft models of drug-resistant KBV20C cells and drug-sensitive parent KB cells. As shown in Figures 4A–C, treatment of nude mice with crizotinib markedly inhibited the resistant KBV20C tumor growth compared with vehicle treatment. Detailed analysis showed that crizotinib treatment significantly reduced the tumor volume by 50% (Figure 4A) and tumor weight by ~40% (Figures 4B,C), relative to the control group. These data show that crizotinib significantly inhibited the growth of KBV20C cells in vivo. Furthermore, whether crizotinib showed a lower sensitizing-effect on drug-sensitive parent KB cells in the in vivo xenograft model (Figures 2D,E, 3B) was tested. As expected, drug-sensitive KB cells showed a VIC treatment time-dependent inhibition of tumor growth compared with the control group, whereas drug-resistant KBV20C cells were not affected by VIC treatment (Figures 4A,D). It was confirmed that crizotinib had a greater effect on KBV20C cells than on KB cells in the in vivo xenograft model (Figures 4A–F). This suggests that crizotinib specifically sensitizes drug-resistant cancer cells. Reference: Front Oncol. 2020 May 12;10:696. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247847/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 10.1 | 22.49 | |
| DMF | 5.0 | 11.10 | |
| DMF:PBS (pH 7.2) (1:1) | 0.5 | 1.11 | |
| Ethanol | 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 |
| Formulation protocol: | 1. Kim KS, Jiang C, Kim JY, Park JH, Kim HR, Lee SH, Kim HS, Yoon S. Low-Dose Crizotinib, a Tyrosine Kinase Inhibitor, Highly and Specifically Sensitizes P-Glycoprotein-Overexpressing Chemoresistant Cancer Cells Through Induction of Late Apoptosis in vivo and in vitro. Front Oncol. 2020 May 12;10:696. doi: 10.3389/fonc.2020.00696. PMID: 32528877; PMCID: PMC7247847. |
| In vitro protocol: | 1. Kim KS, Jiang C, Kim JY, Park JH, Kim HR, Lee SH, Kim HS, Yoon S. Low-Dose Crizotinib, a Tyrosine Kinase Inhibitor, Highly and Specifically Sensitizes P-Glycoprotein-Overexpressing Chemoresistant Cancer Cells Through Induction of Late Apoptosis in vivo and in vitro. Front Oncol. 2020 May 12;10:696. doi: 10.3389/fonc.2020.00696. PMID: 32528877; PMCID: PMC7247847. |
| In vivo protocol: | 1. Kim KS, Jiang C, Kim JY, Park JH, Kim HR, Lee SH, Kim HS, Yoon S. Low-Dose Crizotinib, a Tyrosine Kinase Inhibitor, Highly and Specifically Sensitizes P-Glycoprotein-Overexpressing Chemoresistant Cancer Cells Through Induction of Late Apoptosis in vivo and in vitro. Front Oncol. 2020 May 12;10:696. doi: 10.3389/fonc.2020.00696. PMID: 32528877; PMCID: PMC7247847. |
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