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Chemical Structure| 1374356-45-2 Chemical Structure| 1374356-45-2

Structure of (S)-Crizotinib
CAS No.: 1374356-45-2

Chemical Structure| 1374356-45-2

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(S)-Crizotinib is a potent, selective MTH1 (mutT homolog) inhibitor with an IC50 of 330 nM.

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Product Details of (S)-Crizotinib

CAS No. :1374356-45-2
Formula : C21H22Cl2FN5O
M.W : 450.34
SMILES Code : NC1=NC=C(C2=CN(C3CCNCC3)N=C2)C=C1O[C@H](C4=C(Cl)C=CC(F)=C4Cl)C
MDL No. :MFCD22126092

Safety of (S)-Crizotinib

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H317-H319-H341-H400
Precautionary Statements:P273-P280-P305+P351+P338
Class:9
UN#:3077
Packing Group:

Related Pathways of (S)-Crizotinib

DNA

Isoform Comparison

Biological Activity

Target
  • MTH1

    MTH1, IC50:72 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
H1975 cells 0.625-80 µM 24 hours Measure cell viability, IC50 value was 16.54 μM J Exp Clin Cancer Res. 2017 Sep 7;36(1):120.
HT-1080 cells 1 µM 24 hours Inhibits RSL3-induced ferroptosis Cell Death Discov. 2024 Aug 12;10(1):360.
SK-HEP-1 cells 1 µM 10 hours Inhibits RSL3-induced ferroptosis Cell Death Discov. 2024 Aug 12;10(1):360.
A549 cells 0.625-80 µM 24 hours Measure cell viability, IC50 value was 11.25 μM J Exp Clin Cancer Res. 2017 Sep 7;36(1):120.
U2OS cells 5 µM 24 hours Induces formation of DNA single strand breaks due to activation of endogenous base excision repair Nature. 2014 Apr 10;508(7495):222-7.
NCI-H460 cells 0.625-80 µM 24 hours Measure cell viability, IC50 value was 14.29 μM J Exp Clin Cancer Res. 2017 Sep 7;36(1):120.
BGC-823/R >100 µM (IC50) 24 hours To evaluate the effect of (S)-crizotinib on the viability of resistant gastric cancer cells, results showed that resistant cells had significantly reduced sensitivity to (S)-crizotinib. Cell Death Dis. 2018 May 31;9(6):660.
BGC-823 24.81 µM (IC50) 24 hours To evaluate the effect of (S)-crizotinib on the viability of gastric cancer cells, results showed that (S)-crizotinib significantly reduced cell viability and induced apoptosis. Cell Death Dis. 2018 May 31;9(6):660.
SGC-7901 21.33 µM (IC50) 24 hours To evaluate the effect of (S)-crizotinib on the viability of gastric cancer cells, results showed that (S)-crizotinib significantly reduced cell viability and induced apoptosis. Cell Death Dis. 2018 May 31;9(6):660.
L145 CRC spheroids 10 µM 3 days Assessment of cell viability, results showed (S)-crizotinib significantly reduced cell viability Sci Rep. 2019 Jan 28;9(1):819.
P25T and p26T patient-derived organoids 5 µM 3 days Assessment of cell viability, results showed (S)-crizotinib significantly reduced cell viability Sci Rep. 2019 Jan 28;9(1):819.
SW480 cells 2 µM 3 days Induces DNA damage as indicated by an increase in 53BP1 foci and ATM autophosphorylation Nature. 2014 Apr 10;508(7495):222-7.
SW480 colon carcinoma cells 5 µM 3 hours To evaluate the thermal stabilization effect of (S)-Crizotinib on MTH1 protein, results showed that (S)-Crizotinib significantly stabilized MTH1 protein, while DMSO-treated control cells showed a sharp decline in MTH1 protein content. Nat Methods. 2015 Nov;12(11):1055-7.
SW480 cell lysates 100 µM 30 minutes To assess the target profile of (S)-Crizotinib in cell lysates, results revealed not only MTH1 but also several kinases as targets, suggesting that cellular compartmentalization may affect the compound's target profile. Nat Methods. 2015 Nov;12(11):1055-7.
U251MG cells 0.1 nM to 10 µM 30 minutes Competitive binding assays showed that (S)-Crizotinib has lower affinity for MTH1 with a Ki value of 153.90 ± 20.48 nM Int J Mol Sci. 2020 Nov 23;21(22):8860.
786-O cells 1 µM 4 hours Inhibits RSL3-induced lipid-ROS accumulation Cell Death Discov. 2024 Aug 12;10(1):360.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice (BALB/c nu/nu) Gastric cancer xenograft model Intraperitoneal injection 10 mg/kg (S)-crizotinib, 5 mg/kg MK2206 Once daily for 24 days To evaluate the inhibitory effect of (S)-crizotinib alone or in combination with MK2206 on the growth of gastric cancer xenografts, results showed that the combined treatment significantly inhibited tumor growth. Cell Death Dis. 2018 May 31;9(6):660.
SCID mice SW480 colon carcinoma xenograft model Subcutaneous and oral administration 25 mg/kg (subcutaneous), 50 mg/kg (oral) Once daily for 35 days (subcutaneous), 26 days (oral) Suppresses tumour growth, reduces tumour volume by more than 50% Nature. 2014 Apr 10;508(7495):222-7.
Mice Kidney ischemia-reperfusion injury model Intraperitoneal injection 4 mg/kg and 10 mg/kg Single injection, lasting 24 hours Alleviates renal ischemia-reperfusion injury Cell Death Discov. 2024 Aug 12;10(1):360.
BALB/c nu/nu female mice NCI-H460 xenograft model Intraperitoneal injection 7.5 or 15 mg/kg Once daily for 10 days Evaluate the inhibitory effect of (S)-Crizotinib on tumor growth, results showed significant reductions in tumor volume and weight J Exp Clin Cancer Res. 2017 Sep 7;36(1):120.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.22mL

0.44mL

0.22mL

11.10mL

2.22mL

1.11mL

22.21mL

4.44mL

2.22mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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