NPS-1034
(Synonyms: 2-(4-氟苯基)-N-[3-氟-4-[(3-苯基-1H-吡咯并[2,3-B]吡啶-4-基)氧基]苯基]-2,3-二氢-1,5-二甲基-3-氧代-1H-吡唑-4-甲酰胺) 目录号 : GC14488
A dual MET/AXL inhibitor
Cas No.:1221713-92-3
Sample solution is provided at 25 µL, 10mM.
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NPS-1034 is a MET inhibitor with IC50 of 4 nmol/L [1].
The hepatocyte growth factor receptor tyrosine kinase MET is required for various morphogenetic events and controls the malignant progression of many human tumors. In various advanced human cancer, gene amplification can deregulate MET [1].
In MKN45 and SNU638 cell lines highly expressing the MET gene and p-MET (phosphorylated MET), IC50 values of NPS-1034 to inhibit cell viability were 112.7 and 190.3 nmol, respectively. In AGS, KATOIII, NCI-N87, MKN1, MKN28, and MKN74 cells, the IC50 values of NPS-1034 to inhibit cell viability ranged from 1 μmol to more than 10 μmol. In MKN45 cells, treatment with NPS-1034 dramatically decreased MET phosphorylation (activation). But in MKN28 cells, MET phosphorylation was not dramatically decreased. This meant that the anti-proliferative effect of NPS-1034 was resulted from its inhibition of p-MET [1].
In nude mice bearing MKN45 tumors, after the diameter of MKN45 tumors had reached about 180 mm3, NPS-1034 at a dose of 30 mg/kg or PBS as vehicle was orally administered once daily for 25 days. It was found that NPS-1034 inhibited the proliferation of tumors highly expressing p-MET. Without drug treatment, neovascularization appeared in tumors in nude mice when the tumor volume was >150 mm3. NPS-1034 treatment clearly decreased the vascularization of the tumors in nude mice [1].
Reference:
[1]. Shin JS, Hong SW, Moon JH, et al. NPS-1034, a novel MET inhibitor, inhibits the activated MET receptor and its constitutively active mutants. Investigational new drugs, 2014, 32(3): 389-399.
Cell experiment: | To perform the MTT assay, cells (0.5×104/well) are plated in 96-well sterile plastic plates and allowed to attach overnight. Cells are exposed to varying doses of NPS-1034 in medium containing 1% FBS. After 72 hours, 15 μL of MTT solution (5 mg/mL) is added to each well and plates are incubated for 4 hours. Crystalline formazan is solubilized with 100 μL of a 10% (w/v) SDS solution for 24 hours. Absorbance at 595 nm is read spectrophotometrically using a microplate reader[1]. |
Animal experiment: | Female severe combined immunodeficiency (SCID) mice (17 to 20 g, 6 weeks of age) are used. Tumors are grown by implanting 5×106 cells in Matrigel into the mouse flanks. Treatment of 5 mice per group is started when the tumors have reached a volume of 50 to 100 mm3 with vehicle control or NPS-1034 (10 mg/kg, 5 days a week). NPS-1034 is administered orally. Treatment is stopped at the indicated day and mice are followed-up for tumor recurrence. To measure tumor size, the length (L) and width (W) of the tumor are measured with calipers, and tumor volume (TV) is calculated as TV=(L×W2)/2. Immunohistochemical staining is performed using a specific primary antibody, the EnVision Plus staining kit, and the APO-Direct terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay kit, according to the suppliers' instructions. Quantitative analysis of section staining is performed by counting immunopositive cells in 5 arbitrarily selected fields at ×40 magnification[1]. |
References: [1]. Rho JK, et al. MET and AXL inhibitor NPS-1034 exerts efficacy against lung cancer cells resistant to EGFR kinase inhibitors because of MET or AXL activation. Cancer Res. 2014 Jan 1;74(1):253-62. | |
| Cas No. | 1221713-92-3 | SDF | |
| 别名 | 2-(4-氟苯基)-N-[3-氟-4-[(3-苯基-1H-吡咯并[2,3-B]吡啶-4-基)氧基]苯基]-2,3-二氢-1,5-二甲基-3-氧代-1H-吡唑-4-甲酰胺 | ||
| 化学名 | N-(3-fluoro-4-((3-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy)phenyl)-2-(4-fluorophenyl)-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxamide | ||
| Canonical SMILES | FC1=CC(NC(C2=C(C)N(C)N(C3=CC=C(F)C=C3)C2=O)=O)=CC=C1OC4=CC=NC5=C4C(C6=CC=CC=C6)=CN5 | ||
| 分子式 | C31H23F2N5O3 | 分子量 | 551.54 |
| 溶解度 | DMF: 20 mg/ml,DMSO: 25 mg/ml,DMSO:PBS (pH 7.2)(1:5): 0.16 mg/ml,Ethanol: 1 mg/ml | 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 | 1.8131 mL | 9.0655 mL | 18.1311 mL |
| 5 mM | 0.3626 mL | 1.8131 mL | 3.6262 mL |
| 10 mM | 0.1813 mL | 0.9066 mL | 1.8131 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。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet