Altiratinib (Synonyms: DCC-2701) |
| Catalog No.GC16604 |
c-MET/TIE-2/VEGFR inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1345847-93-9
Sample solution is provided at 25 µL, 10mM.
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Altiratinib (DCC-2701) is a potent inhibitor of c-MET/TIE-2/VEGFR with IC50 values of 2.7, 8.0 and 9.2 nM, respectively [1].
Hepatocyte growth factor receptor (c-MET) is a tyrosine kinase receptor for hepatocyte growth factor and is essential for wound healing and embryonic development. TEK tyrosine kinase (TIE-2) is a receptor for angiopoietin-1 (ANG-1) and is important for endothelial cell-smooth muscle cell communication. VEGFR is a tyrosine kinase receptor for vascular endothelial growth factor that involved in both vasculogenesis and angiogenesis.
Altiratinib (DCC-2701) is a potent c-MET/TIE-2/VEGFR inhibitor. Altiratinib potently inhibited MET kinase and activating oncogenic MET mutations and also inhibited TRKA, TRKB and TRKC kinases with IC50 values of 0.85, 4.6, and 0.83 nM, respectively. In EBC-1 NSCLC and MKN-45 gastric cancer cell lines overexpressing MET, altiratinib inhibited MET phosphorylation with IC50 values of 0.85 and 2.2 nM, respectively. In VEGF-stimulated HUVECs, altiratinib inhibited VEGFR2 phosphorylation with IC50 value of 4.7 nM. In HUVECs and EA.hy926 cells, altiratinib inhibited TIE2 phosphorylation stimulated by ANG-1 with IC50 values of 1.0 and 2.6 nM, respectively [1].
In the MET-amplified MKN-45 xenograft model, altiratinib (30 mg/kg) inhibited MET phosphorylation by >95% for the 24-hour period [1]. In nude mouse xenografted SKOV3 cells, DCC-2701 (10 or 20 mg/kg for 28 days) significantly reduced tumor burden by 53% and 52%, respectively [2].
References:
[1]. Smith BD, Kaufman MD, Leary CB, et al. Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated Drug Resistance via Balanced Inhibition of MET, TIE2, and VEGFR2. Mol Cancer Ther, 2015.
[2]. Kwon Y, Smith BD, Zhou Y, et al. Effective inhibition of c-MET-mediated signaling, growth and migration of ovarian cancer cells is influenced by the ovarian tissue microenvironment. Oncogene, 2015, 34(2): 144-153.
Cell experiment: | Altiratinib is dispensed into assay plates. Cells are added to 96-well (EBC-1, M-NFS-60, and SK-MEL-28: 2,500 cells/well; MKN-45: 5,000 cells/well; MV-4-11: 10,000 cells/well) or 384-well plates (A375 and HCT-116: 625 cells/well; BT-474, KM-12, PC-3, and U-87-MG: 1,250 cells/well). Plates are incubated for 72 hours. Viable cells are quantified using resazurin using a plate reader with excitation at 540 nm and emission at 600 nm[1]. |
Animal experiment: | Mice: Female nude mice are inoculated subcutaneously. On days 9 to 10, when tumor volumes reached 326 mg on average, mice are randomly assigned to groups and dosed once orally with 0.4% HMPC, (n=3); Altiratinib at 30 mg/kg (n=21); or Altiratinib at 10 mg/kg (n=21). At specified time points, whole blood and tumors are collected. Pharmacokinetic analysis is performed. Tumor samples are processed in the Western blot assay methods[1]. |
References: [1]. Smith BD, et al. Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated DrugResistance via Balanced Inhibition of MET, TIE2, and VEGFR2. Mol Cancer Ther. 2015 Sep;14(9):2023-34. | |
| Cas No. | 1345847-93-9 | SDF | |
| Synonyms | DCC-2701 | ||
| Chemical Name | N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide | ||
| Canonical SMILES | FC1=CC=C(NC(C2(C(NC3=C(F)C=C(OC4=CC(NC(C5CC5)=O)=NC=C4)C(F)=C3)=O)CC2)=O)C=C1 | ||
| Formula | C26H21F3N4O4 | M.Wt | 510.46 |
| Solubility | ≥ 21.55mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.959 mL | 9.7951 mL | 19.5902 mL |
| 5 mM | 0.3918 mL | 1.959 mL | 3.918 mL |
| 10 mM | 0.1959 mL | 0.9795 mL | 1.959 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 31 reference(s) in Google Scholar.)
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