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| 5mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
(S)-crizotinib, the (S)-enantiomer of crizotinib, is a novel and potent MTH1 (NUDT1) inhibitor with IC50 of 72 nM in a cell-free assay. Similar to SCH51344, it effectively prevented the colony formation of PANC1 cells with the KRAS mutation and SW480 cells. Additionally, in vitro Kd measurements revealed that (S)-crizotinib had significantly lower potency than (R)-enantiomer against the known targets ALK, MET, and ROS1. The most toxic effects of (S)-crizotinib were observed in SV40T and KRASV12 cells, and these cells did not exhibit any discernible effects on the proliferation of SW480 cells.
| Targets |
PTEN (IC50 = 330 nM); NUDIX1
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| ln Vitro |
(S)-crizotinib disrupts nucleotide pool homeostasis via MTH1 inhibition, induces an increases DNA single-strand breaks, and turns on DNA repair in human colon carcinoma cells.[1]
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| ln Vivo |
(S)-Crizotinib (50 mg/kg, orally, daily) impairs tumor growth in an SW480 colon carcinoma xenograft model. [1]
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| Enzyme Assay |
Half-maximal inhibitory concentrations (IC50) are determined using a luminescence-based assay with some minor modifications. Assay buffer, which contains 100 mM Tris-acetate pH 7.5, 40 mM NaCl, 10 mM Mg(OAc)2 containing 0.005% Tween-20, and 2 mM dithiothreitol (DTT), is used to dissolve serial dilutions of compounds. Plates are shaken for 15 minutes at room temperature after being added with MTH1 recombinant protein (final concentration: 2 nM). After addition of the substrate dGTP (final concentration 100 µM), 8-oxo-dGTP (final concentration 13.2 µM), or 2-OH-dATP (final concentration 8.3 µM) the generation of pyrophosphate (PPi) as a result of nucleotide triphosphate hydrolysis by MTH1 is monitored over a time course of 15 min using the PPi Light Inorganic Pyrophosphate Assay kit. By fitting a dose-response curve to the data points using nonlinear regression analysis and the GraphPad Prism program, IC50 values are calculated.
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| Cell Assay |
One day before treatment, cells are seeded per well in six-well plates and incubated for 24 h. The next day DMSO (equal to highest amount of compound dilution, maximum 0.2%) or compounds in increasing concentrations were added and cells incubated at 37 °C, 5% CO2, for 7-10 days. After washing with PBS, cells are fixed with ice-cold methanol, stained with crystal violet solution (0.5% in 25% methanol) and left to dry overnight. For quantification of results, ultraviolet absorbance of crystal violet is determined at 595 nm following solubilisation by 70% ethanol. Data are analysed using nonlinear regression analysis using the GraphPad Prism software.
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| Animal Protocol |
In six-well plates, cells are plated one day prior to treatment and incubated for 24 hours. The cells were then incubated at 37 °C with 5% CO2 for 7–10 days. The following day, DMSO (equivalent to the highest amount of compound dilution, maximum 0.2%) or compounds were added. Crystal violet solution (0.5% in 25% methanol) is used to stain cells after they have been washed with PBS. Cells are then allowed to dry overnight before being fixed with ice-cold methanol. Crystal violet's ultraviolet absorbance is measured at 595 nm for results quantification after being solubilized in 70% ethanol. GraphPad Prism software is used to analyze data using nonlinear regression.
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| References |
| Molecular Formula |
C21H22CL2FN5O
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|---|---|---|
| Molecular Weight |
450.34
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| Exact Mass |
449.1185
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| Elemental Analysis |
C, 56.01; H, 4.92; Cl, 15.74; F, 4.22; N, 15.55; O, 3.55
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| CAS # |
1374356-45-2
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
C[C@@H](C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N
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| InChi Key |
KTEIFNKAUNYNJU-LBPRGKRZSA-N
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| 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-/m0/s1
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| Chemical Name |
3-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine
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| Synonyms |
S-Crizotinib; PF-2341066; PF2341066; PF02341066; PF-02341066; PF 2341066
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~42 mg/mL (~93.3 mM)
Water: <1 mg/mL Ethanol: ~22 mg/mL (~48.9 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.78 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (2.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2205 mL | 11.1027 mL | 22.2054 mL | |
| 5 mM | 0.4441 mL | 2.2205 mL | 4.4411 mL | |
| 10 mM | 0.2221 mL | 1.1103 mL | 2.2205 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02761057 | Active Recruiting |
Drug: Crizotinib Drug: Savolitinib |
Stage III Renal Cell Cancer AJCC v7 Stage IV Renal Cell Cancer AJCC v7 |
National Cancer Institute (NCI) |
April 5, 2016 | Phase 2 |
| NCT04439253 | Active Recruiting |
Drug: Crizotinib | Advanced Lymphoma Refractory Lymphoma |
National Cancer Institute (NCI) |
August 12, 2015 | Phase 2 |
| NCT02767804 | Active Recruiting |
Drug: crizotinib Drug: X-396 (ensartinib) |
Non-small Cell Lung Cancer | Xcovery Holding Company, LLC | June 2016 | Phase 3 |
| NCT03052608 | Active Recruiting |
Drug: Lorlatinib Drug: Crizotinib |
Carcinoma, Non-Small-Cell Lung | Pfizer | April 27, 2017 | Phase 3 |
| NCT02465060 | Active Recruiting |
Drug: Afatinib Drug: Adavosertib |
Bladder Carcinoma Breast Carcinoma |
National Cancer Institute (NCI) |
August 12, 2015 | Phase 2 |
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