Altiratinib
(Synonyms: DCC-2701) 目录号 : GC16604
A multiple kinase inhibitor
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 | |
| 别名 | DCC-2701 | ||
| 化学名 | 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 | ||
| 分子式 | C26H21F3N4O4 | 分子量 | 510.46 |
| 溶解度 | ≥ 21.55mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet