| 名稱 | Pazopanib Hydrochloride |
| 描述 | Pazopanib Hydrochloride (Votrient HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. |
| 細胞實驗 | Phosphorylation of VEGFR2 is assessed in HUVEC stimulated with VEGF. HUVEC are plated in type-I collagen-coated 10 cm plates in Clonetics EGM-MV medium at 1.0-1.5 × 106 cells/plate. After 24 hours, the confluent cells are serum starved overnight by replacing the growth medium with Clonetics EBM medium containing 0.1% BSA, 500 μg/mL hydrocortisone. Cells are treated with Pazopanib at various concentrations for 1 hour, followed by addition of 10 ng/mL VEGF or vehicle for 10 min. Cells are solubilized in lysis buffer. VEGFR2 is immunoprecipitated using antiflk-1 antibody and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting and detection with antiflk-1 or with antiphosphotyrosine (anti-P-tyr-biotin) antibody. The VEGFR2 phosphorylation level is quantified by densitometry and normalized to the total VEGFR2 level. (Only for Reference) |
| 激酶實驗 | Kinase enzyme assays: VEGFR enzyme assays for VEGGR1, VEGFR2, and VEGFR3 are run in homogeneous time-resolved fluorescence (HTRF) format in 384-well microtiter plates using a purified, baculovirus-expressed glutathione-S-transferase (GST) fusion protein encoding the catalytic c-terminus of human VEGFR receptor kinases 1, 2, or 3. Reactions are initiated by the addition of 10 μL of activated VEGFR2 kinase solution [final concentration, 1 nM enzyme in 0.1 M HEPES, pH 7.5, containing 0.1 mg/mL bovine serum albumin (BSA), 300 μM dithiothreitol (DTT)] to 10 μL substrate solution [final concentration, 360 nM peptide, (biotin-aminohexyl-EEEEYFELVAKKKK-NH2), 75 μM ATP, 10 μM MgCl2], and 1 μL of titrated Pazopanib in DMSO. Plates are incubated at room temperature for 60 min, and then the reaction is quenched by the addition of 20 μL of 100 mM ethylene diamine tetraacetic acid (EDTA). After quenching, 20 μL HTRF reagents (final concentration, 15 nM Streptavidin-linked allophycocyanin, 1 nM Europium-labeled antiphosphotyrosine antibody diluted in 0.1 mg/mL BSA, 0.1 M HEPES, pH 7.5) is added and the plates incubated for a minimum of 10 min. The fluorescence at 665 nM is measured with a Wallac Victor plate reader using a time delay of 50 μs. |
| 體外活性 | Pazopanib以8 nM的IC50強效抑制VEGF誘導的VEGFR2在HUVEC細胞中的磷酸化。[1] Pazopanib對包括SYO-1和HS-SY-II細胞在內(nèi)的所有滑膜肉瘤細胞系顯示出劑量依賴性的生長抑制。即使在Pazopanib濃度為1μg/mL時，SYO-1和HS-SY-II細胞的增殖也受到抑制，并且在5μg/mL時完全停止。Pazopanib引發(fā)G1階段停滯，從而抑制滑膜肉瘤細胞的生長。與對照組相比，Pazopanib處理的SYO-1細胞中Akts、GSK-3β、JNKs、p70 S6 Kinase和mTOR的磷酸化受到抑制。[2] 當Pazopanib濃度在20μg/mL到22.5μg/mL之間時，RPE細胞存活率呈現(xiàn)增加的減少。[3] |
| 體內(nèi)活性 | 經(jīng)30mg/kg或100mg/kg Pazopanib處理的小鼠與接受安慰劑或10mg/kg Pazopanib處理的小鼠相比，腫瘤負擔顯著減少。Pazopanib的治療具有良好的耐受性，各組小鼠之間的體重無顯著差異。[2] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 7.5 mg/mL (15.82 mM), Sonication is recommended.
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| 關鍵字 | inhibit | CD117 | CSF1R | Vascular endothelial growth factor receptor | colony stimulating factor 1 receptor | FGFR | VEGFR | Platelet-derived growth factor receptor | GW 786034 | CSF-1R | SCFR | GW-786034 | Inhibitor | Pazopanib Hydrochloride | Autophagy | Pazopanib | c-Fms | PDGFR | c-Kit | Fibroblast growth factor receptor | CSF-1 receptor |
| 相關產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Gefitinib | Aceglutamide | Hydroxychloroquine | Ferulic Acid | Curcumin | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
| 相關庫 | 經(jīng)典已知活性庫 | 抗癌活性化合物庫 | 抗癌上市藥物庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | FDA 上市藥物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |