Pazopanib (GW-786034)
(Synonyms: 帕唑帕尼; GW786034) 目录号 : GC16327
A multi-kinase inhibitor
Cas No.:444731-52-6
Sample solution is provided at 25 µL, 10mM.
Pazopanib is a potent and selective second generation multi-targeted receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit tyrosine kinases. It is involved in inhibiting signaling pathways, angiogenesis, and cell proliferation. Pazopanib exhibited excellent anti-angiogenic and anti-tumor activity and synergism was observed in combination with chemotherapeutic drugs in several mouse models of a variety of tumors, accompanied by desirable pharmacokinetics and oral bioavailability. It inhibits the intracellular tyrosine kinase portion of all the VEGFR subtypes, and exhibits distinct pharmacokinetic and toxicity profiles compared with other agents among VEGF signaling pathway inhibitors. Recent studies elucidated its importance of signaling cascades related to angiogenesis in the management of RCC.
Reference
[1].Sonpavde G, Hutson T E. Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Current oncology reports. 2007; 9(2): 115 - 119.
[2].Podar K, Tonon G, Sattler M, et al. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proceedings of the National Academy of Sciences. 2006; 103(51): 19478 - 19483.
| Cell experiment: [1] | |
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Cell lines |
Primary human brain microvascular endothelial cells (HBMEC) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
IC50: 2 μM, 48 hours |
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Applications |
The IC50 for pazopanib for anchorage-dependent growth was 2 μM and 1 μM after 48 h and 72 h, respectively. Pazopanib abrogated the phosphorylation of VEGFR2 with disruption of downstream PLCγ1. It also disrupted the Ras-Raf-ERK pathway through decreased phosphorylated MEK1/2 and ERK1/2 and affected the phosphorylation of 70S6K. Our findings confirmed that pazopanib targeted endothelial cells, affecting cell growth, VEGFR-induced signaling, and tube formation. |
| Animal experiment: [2] | |
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Animal models |
Immune-deficient beige-nude-xid (BNX) mice injected with MM.1S cells |
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Dosage form |
Oral administration, 30 mg/kg and 100 mg/kg, daily for five weeks |
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Applications |
Tumor growth in treated mice was significantly delayed (30 mg/kg) or almost totally inhibited (100 mg/kg) compared with the control group. However, tumors rapidly regrew after cessation of treatment at day 30. Using Kaplan–Meier and log-rank analysis, the mean overall survival (OS) was 20 days in the control cohort versus 41 days and 51 days in groups treated with 30 mg/kg and 100 mg/kg pazopanib, respectively. Statistically significant prolongation in mean OS compared with control mice was observed in animals treated with 30 mg/kg and 100 mg/kg. Importantly, treatment with either the vehicle alone or pazopanib did not affect 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] Gril B, Palmieri D, Qian Y, et al. Pazopanib reveals a role for tumor cell B-Raf in the prevention of HER2+ breast cancer brain metastasis. Clinical Cancer Research, 2011, 17(1): 142-153. [2] Podar K, Tonon G, Sattler M, et al. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proceedings of the National Academy of Sciences, 2006, 103(51): 19478-19483. | |
| Cas No. | 444731-52-6 | SDF | |
| 别名 | 帕唑帕尼; GW786034 | ||
| 化学名 | 5-[[4-[(2,3-dimethylindazol-6-yl)-methylamino]pyrimidin-2-yl]amino]-2-methylbenzenesulfonamide;hydrochloride | ||
| Canonical SMILES | CC1=C(C=C(C=C1)NC2=NC=CC(=N2)N(C)C3=CC4=NN(C(=C4C=C3)C)C)S(=O)(=O)N.Cl | ||
| 分子式 | C21H23N7O2S | 分子量 | 437.52 |
| 溶解度 | ≥ 10.95 mg/mL in DMSO | 储存条件 | Desiccate 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 | 2.2856 mL | 11.428 mL | 22.8561 mL |
| 5 mM | 0.4571 mL | 2.2856 mL | 4.5712 mL |
| 10 mM | 0.2286 mL | 1.1428 mL | 2.2856 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