客户使用产品发表文献 1 篇

Int Immunopharmacol 116 (2023): 109735.PMID:36716517

产品文档

Quality Control & SDS

View current batch:

Purity: >99.50%

实验参考方法

Cell experiment: [1]
Cell lines	Primary human brain microvascular endothelial cells (HBMEC)
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.
Reaction Conditions	IC50: 2 μM, 48 hours
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]
Animal models	Immune-deficient beige-nude-xid (BNX) mice injected with MM.1S cells
Dosage form	Oral administration, 30 mg/kg and 100 mg/kg, daily for five weeks
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.
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.
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.

产品描述

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.

Chemical Properties

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。
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。

溶解性数据

制备储备液
		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

摩尔浓度计算器
稀释计算器
分子量计算器

计算

动物体内配方计算器 (澄清溶液)

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，注：如该浓度超过该批次药物DMSO溶解度，请先联系GLPBIO）；

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。

注意：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。

Research Update

Determination of pazopanib (GW-786034) in mouse plasma and brain tissue by liquid chromatography-tandem mass spectrometry (LC/MS-MS)

A simple, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC/MS-MS) method has been developed and validated for the quantitative determination of pazopanib in mouse plasma and brain tissue homogenate. Single liquid-liquid extraction step with ethyl acetate was employed for analysis of pazopanib and the internal standard (IS); vandetanib. HPLC separation was performed on an XTerra(?) MS C18 column 50 mm × 4.6 mm, 5.0 μm. The mobile phase consisted of 70% acetonitrile and 30% water with 0.1% formic acid, pumped at a flow rate of 0.25 ml/min. Analysis time was 3.5 min per run and both the analyte and IS eluted within 1.8-2.0 min. Multiple reactions monitoring (MRM) mode was utilized to detect the compounds of interest. The mass spectrometer was operated in the positive ion mode for detection. The precursor to product ions (Q1→Q3) selected for pazopanib and internal standard during quantitative optimization were (m/z) 438.1→357.2 and 475.0→112.2 respectively. The calibration curves were linear over the range of 3.9-1000 ng/ml in both biological matrices. Lower limit of quantification (LLOQ) for mouse plasma and brain tissue was 3.9 ng/ml. The values for inter and intra day precision and accuracy were well within the ranges acceptable for analytical assessment (<15%). This method was applied to determine brain to plasma concentration ratio and relevant pharmacokinetic parameters of pazopanib after a single intravenous dose of 5 mg/kg in FVB wild type mice.

Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma

Background: The recent approvals of sunitinib, sorafenib and temsirolimus have revolutionized the management of renal cell carcinoma (RCC). Pazopanib (GW-786034) is a second-generation multitargeted tyrosine kinase inhibitor against VEGFR-1, 2 and 3, platelet-derived growth factor receptor (PDGFR)-alpha, PDGFR-beta and c-kit.
Objective: Data supporting the development of pazopanib for RCC are reviewed.
Methods: Preclinical and clinical data available for pazopanib are presented.
Results: Preclinical evaluation has revealed excellent anti-angiogenic and anti-tumor activity in several mouse models. A Phase II clinical trial of pazopanib in untreated or cytokine/bevacizumab pretreated RCC has demonstrated promising activity accompanied by a favorable toxicity profile. A placebo-controlled Phase III trial is ongoing in untreated or cytokine-treated patients with RCC. Ongoing trials are further evaluating pazopanib in a variety of other malignancies.

Pazopanib for the treatment of renal cell carcinoma and other malignancies

Pazopanib (GW-786034) is a second-generation multitargeted tyrosine kinase inhibitor against VEGFR1, -2 and -3, PDGFRalpha, PDGFRbeta and c-Kit. Preclinical evaluation has revealed excellent anti-angiogenic and antitumor activity in several tumors. A phase II clinical trial of pazopanib in untreated or cytokine/bevacizumab-pretreated renal cell carcinoma (RCC) has demonstrated promising activity accompanied by a favorable toxicity profile. A placebo-controlled phase III trial in untreated or cytokine-treated patients with RCC demonstrated a significant improvement in progression-free survival. Ongoing trials are further evaluating pazopanib in a variety of other malignancies.

Pazopanib (GW-786034)

Customer Reviews

B1