LY2801653
(Synonyms: 梅沙替尼,LY-2801653;LY 2801653) 目录号 : GC11057
A MET kinase inhibitor
Cas No.:1206799-15-6
Sample solution is provided at 25 µL, 10mM.
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LY2801653 is a potent and orally bioavailable inhibitor of c-MET kinase with IC50 value of 2 nM [1].
C-MET kinase is also known as hepacyte growth factor receptor (HGFR), which is a membrane-associated tyrosine kinase receptor. HGF is the only ligand for this receptor. The binding of HGF induces conformational changes of c-MET and thus activate tyrosine kinase activity, to process downstream signaling. C-MET signaling regulate various cellular functions including cell proliferation, survival and apoptosis, and abnormal activation of c-MET kinase may trigger tumor growth, angiogenesis and metastasis.
Biochemical study and crystallization study identified LY2801653 was a potent ATP-competitive inhibitor of c-MET kinase, where the inhibition was completed by suppression of c-MET kinase phosphorylation [1]. In vitro study showed that 0.01-10 μM LY2801653 was able to completely block HGF-induced DU-145 cell scattering regulated by c-MET kinase, which demonstrated the inhibition of c-MET kinase activity. When LY2801653 was screened with a panel of cell lines, it was found more potent anti-proliferative activity of LY2801653 in those cell lines with MET gene expression than without MET gene expression [2].
Mice bearing U-87MG xenograft were treated with low dose (1.3 mg/kg) and high dose (12 mg/kg) LY2801653 once daily for 28 days, and the tissues were characterized. It was found that low dose treatment resulted in a trend of reducing the area of c-MET kinase-associated apoptosis while the high dose treatment resulted in significant reduced apoptosis area. Additionally, high dose resulted in the suppression of c-MET kinase-associated angiogenesis, and vessels tend to be normalized [2].These observations demonstrated the LY2801653 was able to disrupt c-MET kinase downstream signaling via inhibiting the c-MET kinase activity.
Reference:
[1] Yan S B et al. , LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs. 2012, 31: 833-844.
| Cell experiment [1]: | |
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Cell lines |
Human NSCLC H441 cell lines |
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Preparation method |
The solubility of this compound in DMSO is > 27.7mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.01-10 µM, 2 h |
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Applications |
In H441 cells, LY2801653 inhibited phosphorylation and downstream signaling of MET leading to a blockage of MET pathway. LY2801653 also inhibited proliferation, growth, migration and invasion of H441 cells. |
| Animal experiment [2]: | |
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Animal models |
Six-week-old female severe combined immunodeficient (SCID) mice |
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Dosage form |
Oral administration, 20 mg/kg |
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Application |
LY2801653 inhibited growth of tumors, significantly inhibiting cells mitotic and angiogenesis. Treatment with LY2801653 reduced A549-luc-C8 tumor growth in SCID mice significantly comparing to control group and no change in body weight. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Wu W, Bi C, Credille K M, et al. Inhibition of Tumor Growth and Metastasis in Non–Small Cell Lung Cancer by LY2801653, an Inhibitor of Several Oncokinases, Including MET[J]. Clinical Cancer Research, 2013, 19(20): 5699-5710. [2]. Kawada I, Hasina R, Arif Q, et al. Dramatic Antitumor Effects of the Dual MET/RON Small-Molecule Inhibitor LY2801653 in Non–Small Cell Lung Cancer[J]. Cancer research, 2014, 74(3): 884-895. | |
| Cas No. | 1206799-15-6 | SDF | |
| 别名 | 梅沙替尼,LY-2801653;LY 2801653 | ||
| 化学名 | N-[3-fluoro-4-[1-methyl-6-(1H-pyrazol-4-yl)indazol-5-yl]oxyphenyl]-1-(4-fluorophenyl)-6-methyl-2-oxopyridine-3-carboxamide | ||
| Canonical SMILES | CC1=CC=C(C(=O)N1C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C=C5C(=C4)C=NN5C)C6=CNN=C6)F | ||
| 分子式 | C30H22F2N6O3 | 分子量 | 552.53 |
| 溶解度 | ≥ 27.65 mg/mL in DMSO, ≥ 5.02 mg/mL in EtOH with ultrasonic and warming | 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 | 1.8099 mL | 9.0493 mL | 18.0986 mL |
| 5 mM | 0.362 mL | 1.8099 mL | 3.6197 mL |
| 10 mM | 0.181 mL | 0.9049 mL | 1.8099 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet