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(S)-Crizotinib
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
(S)-Crizotinib图片
CAS NO:1374356-45-2
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)450.34
FormulaC21H22Cl2FN5O
CAS No.1374356-45-2
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 42 mg/mL (93.3 mM)
Water: <1 mg/mL
Ethanol: 22 mg/mL (48.9 mM)
SMILESNC1=NC=C(C2=CN(C3CCNCC3)N=C2)C=C1O[C@H](C4=C(Cl)C=CC(F)=C4Cl)C
SynonymsS-Crizotinib

Chemical Name: 3-[(1S)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-2-pyridinamine

InChi Key: KTEIFNKAUNYNJU-LBPRGKRZSA-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-/m0/s1

SMILES Code: NC1=NC=C(C2=CN(C3CCNCC3)N=C2)C=C1O[C@H](C4=C(Cl)C=CC(F)=C4Cl)C

实验参考方法
In Vitro

In vitro activity: (S)-crizotinib disrupts nucleotide pool homeostasis via MTH1 inhibition, induces an increase in DNA single-strand breaks, and activates DNA repair in human colon carcinoma cells.


Kinase Assay: Half-maximal inhibitory concentrations (IC50) are determined using a luminescence-based assay with some minor modifications. Briefly, serial dilutions of compounds are dissolved in assay buffer (100 mM Tris-acetate pH 7.5, 40 mM NaCl and 10 mM Mg(OAc)2 containing 0.005% Tween-20 and 2 mM dithiothreitol (DTT). Upon addition of MTH1 recombinant protein (final concentration 2 nM), plates are incubated on a plate shaker for 15 min at room temperature. 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. IC50 values are determined by fitting a dose-response curve to the data points using nonlinear regression analysis using the GraphPad Prism software.


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.

In Vivo(S)-Crizotinib (50 mg/kg, orally, daily) impairs tumor growth in an SW480 colon carcinoma xenograft model
Animal modelSW480 colon carcinoma xenograft mouse model.
Formulation & DosageFormulated in 1% DMSO, 10% ethanol, 10% Cremophor, 10% Tween 80, 69% PBS; 50 mg/kg daily; p.o.
References

Nature. 2014 Apr 10;508(7495):222-7.