Crizotinib (PF-02341066) is a potent, orally bioavailable, ATP-competitive small-molecule inhibitor of c-Met kinase and ALK (anaplastic lymphoma kinase) with IC50 values to be 4 and 25 nM for C-Met and ALK resepectively.PF-2341066 (Crizotinib) potently inhibited cell proliferation, which was associated with G1-S–phase cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells (IC50 values=30 nM) 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 values=25–50 nM).
Cancers (Basel). 2021 Jul 9;13(14):3441.
Generation and Characterization of a New Preclinical Mouse Model of EGFR-Driven Lung Cancer with MET-Induced Osimertinib Resistance
Crizotinib (PF-02341066) purchased from AbMole
Biomed Chromatogr. 2020 Apr 23;e4863.
A Novel LC-MS/MS Method for the Determination of Ziritaxestat in Rat Plasma and Its Pharmacokinetic Study
Crizotinib (PF-02341066) purchased from AbMole
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Source | Drug Des Devel Ther (2015). Figure 2. PF-2341066 |
| Method | Matrigel invasion assay | |
| Cell Lines | NPC cell | |
| Concentrations | 0.67±0.07 mm | |
| Incubation Time | 48 h | |
| Results | Distance of NPC cell scramble at 48 hours was 0.99±0.11 mm in plates of PF-2341066 alone, 0.67±0.07 mm in cisplatin alone, and 0.33±0.05 mm in combination, (P,0.05) |
 |
Source | Drug Des Devel Ther (2015). Figure 1. PF-2341066 |
| Method | Cell proliferation assay | |
| Cell Lines | HNE -1 cells | |
| Concentrations | 0.79±0.21 μmol/L | |
| Incubation Time | 48 h | |
| Results | The half maximal inhibitory concentration of PF-2341066 alone is 0.79±0.21 μmol/L, while combination with cisplatin is 0.41±0.13 μmol/L. The inhibition rate increased by 23.4% and showed certain synergistic effects |
| Cell Experiment | |
|---|---|
| Cell lines | Karpas299, SUDHL-1, or U-937 cells |
| Preparation method | Cell Proliferation/Survival Assays. Cells were seeded in 96-well plates at low density at 37°C in medium supplemented with 10% FBS (growth medium) and after 24 h were switched to low serum medium (2% FBS). Designated concentrations of PF-2341066 were added to each well and cells were incubated at 37°C for 72 h. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Promega) was done to determine the relative cell numbers. IC50 values were calculated by concentration-response curve fitting using a Microsoft Excel–based four-parameter analytic method. |
| Concentrations | 0~1µM |
| Incubation time | 72h |
| Animal Experiment | |
|---|---|
| Animal models | S.c. Xenograft Models in Athymic Mice |
| Formulation | sterile water |
| Dosages | 100mg/kg daily |
| Administration | oral gavage |
| Molecular Weight | 450.34 |
| Formula | C21H22Cl2FN5O |
| CAS Number | 877399-52-5 |
| Solubility (25°C) | DMSO 11 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[1] Foyil KV, et al. Cancer J. Brentuximab vedotin and crizotinib in anaplastic large-cell lymphoma.
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