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Chemical Structure| 1365267-27-1 Chemical Structure| 1365267-27-1

Structure of X-376
CAS No.: 1365267-27-1

Chemical Structure| 1365267-27-1

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Ensartinib is a potent inhibitor ofALK, which is used to treat non-small-cell lung cancer.

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Product Details of X-376

CAS No. :1365267-27-1
Formula : C25H25Cl2FN6O3
M.W : 547.41
SMILES Code : O=C(C1=NN=C(N)C(O[C@@H](C2=C(Cl)C=CC(F)=C2Cl)C)=C1)NC3=CC=C(C(N4CCN(C)CC4)=O)C=C3
MDL No. :MFCD25976868
InChI Key :ONPGOSVDVDPBCY-CQSZACIVSA-N
Pubchem ID :56960447

Safety of X-376

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of X-376

RTK

Isoform Comparison

Biological Activity

Description
X-376 is identified as a highly potent and specific inhibitor of the ALK tyrosine kinase (TKI), boasting an IC50 value of 0.61 nM, making it less effective against MET with an IC50 of 0.69 nM. Its anticancer efficacy is pronounced[1].

In Vitro:

Cell Line
Concentration Treated Time Description References
Human liver microsomes 30 mM 120 minutes In vitro phase-I metabolic reactions were performed to generate X-376 reactive intermediates, which cannot be detected directly as they are unstable. Utilizing LC-MS/MS, we characterized X-376 metabolites and checked for the reactive electrophile generation using nucleophilic trapping agents, namely, potassium cyanide and GSH, which form stable adducts for characterization by mass spectrometry. RSC Adv. 2020 Feb 3;10(9):5412-5427
MKN-45 gastric carcinoma cells 150 nM 72 hours Assess growth inhibition, X-376 had weaker inhibition on MET Cancer Res. 2011 Jul 15;71(14):4920-31
SY5Y neuroblastoma cells 142 nM 72 hours Assess growth inhibition, X-376 was more potent than PF-1066 Cancer Res. 2011 Jul 15;71(14):4920-31
SUDHL-1 lymphoma cells 32 nM 72 hours Assess growth inhibition, X-376 was more potent than PF-1066 Cancer Res. 2011 Jul 15;71(14):4920-31
H2228 lung cancer cells 57 nM 72 hours Assess growth inhibition, X-376 was more potent than PF-1066 Cancer Res. 2011 Jul 15;71(14):4920-31
H3122 lung cancer cells 77 nM 72 hours Assess growth inhibition, X-376 was more potent than PF-1066 Cancer Res. 2011 Jul 15;71(14):4920-31

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice H3122 xenograft model Oral gavage 50mg/kg Twice daily for 3 weeks Evaluate anti-tumor activity and pharmacokinetic properties, X-376 significantly delayed tumor growth Cancer Res. 2011 Jul 15;71(14):4920-31

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.83mL

0.37mL

0.18mL

9.13mL

1.83mL

0.91mL

18.27mL

3.65mL

1.83mL

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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