KTN0073
KTN0073 is a high-affinity MET receptor tyrosine kinase inhibitor. KTN0073 can be used in studies related to non-small cell lung cancer and human cancers driven by HGF, MET amplification, or exon 14 mutation. KTN0073 binds to the Sema/PSI domain to block the HGF-MET interaction, and induces ubiquitination and degradation of oncogenic MET receptors via an HGF-independent pathway, thereby inhibiting MET-dependent signal transduction. KTN0073 exhibits significant antitumor activity in vivo, and its tumor suppressive activity is superior to that of the IgG1 subtype when grafted to the IgG2 constant region.
For research use only. We do not sell to patients.
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Human IgG2 kappa
Human
KTN0073 (Serial dilutions; 2 hours) potently inhibits HGF-stimulated MET phosphorylation in A549 cells with an IC50 ranging from 40 to 217 pmol/L[2].
KTN0073 (Up to 100 nmol/L; 4 to 5 days) inhibits HGF-induced U87MG cell spheroid proliferation without exhibiting agonistic activity[2].
KTN0073 (1 nmol/L; 2 hours) inhibits HGF-stimulated phosphorylation of MET, Akt, and MAPK in A549 cells to levels comparable to crizotinib[2].
KTN0073 (1 nmol/L; 15 minutes) induces potent ubiquitination of MET in A549 cells after 15 minutes[2].
KTN0073 (1 nmol/L; 24 hours) does not induce MET shedding in A549 cells after 24 hours, unlike PMA treatment[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:U87MG cells
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Concentration:Up to 100 nmol/L
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Incubation Time:4 to 5 days (with HGF)
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Result:Inhibited HGF-induced U87MG spheroid proliferation with no agonistic activity observed in the absence of exogenous HGF.
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Cell Line:A549 cells
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Concentration:1 nmol/L
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Incubation Time:2 hours (preincubated prior to 10-minute HGF stimulation)
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Result:Inhibited HGF-induced phosphorylation of MET, Akt, and MAPK to levels comparable to the MET kinase inhibitor crizotinib.
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Cell Line:SNU5 cells (MET-amplified), EBC1 cells (MET-amplified)
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Concentration:Serial dilutions
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Incubation Time:5 days
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Result:Induced 86% and 97% inhibition of cell proliferation in SNU5 and EBC1 cells, respectively, whereas KTN0073-IgG1 and KTN0073-IgG4 showed no inhibition.
KTN0073 (3 mg/kg; i.p.; 2 doses on days 0 and 3) induces significant MET protein degradation in U87MG glioma xenografts, reducing MET-positive staining to 6.7%[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (female, 6 to 8 weeks old, subcutaneous xenograft with human U87MG glioma cells)[2]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:i.p.; biweekly
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Result:Induced potent growth inhibition of established U87MG tumors.
Resulted in tumor growth inhibition comparable to 50 mg/kg crizotinib at 30 mg/kg.
Was well-tolerated with no weight loss or observational toxicity reported.
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Animal Model:BALB/c nude mice (female, 6 to 8 weeks old, subcutaneous xenograft with human U87MG glioma cells)[2]
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Dosage:3 mg/kg
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Administration:i.p.; 2 doses on days 0 and 3
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Result:Reduced MET-positive staining to 6.7% in treated tumors, compared to 37.4% for PBS-treated tumors and 34.6% for control antibody-treated tumors.
HGFR/c-Met
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
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Product Image
ELISA, FACS, Functional assay
Chemical Information
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Stella GM, et al. Brain Metastases from Lung Cancer: Is MET an Actionable Target?. Cancers (Basel). 2019;11(3):271. Published 2019 Feb 26. [Content Brief]
[2]. Yang Y, et al. Antitumor Properties of an IgG2-Enhanced Next-Generation MET Monoclonal Antibody That Degrades Wild-Type and Mutant MET Receptors. Cancer Res. 2016;76(19):5788-5797. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KTN0073 Related Classifications
HY-P992396 Related Classifications
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