| 名稱 | (Z)-Semaxinib |
| 描述 | (Z)-Semaxinib (SU5416) is a potent and selective VEGFR(Flk-1/KDR) inhibitor (IC50: 1.23 μM), 20-fold more selective for VEGFR over PDGFRβ, no inhibition for FGFR, InsR, and EGFR. (Z)-Semaxinib is a quinolone derivative with potential antineoplastic activity. |
| 細(xì)胞實(shí)驗(yàn) | HUVECs are plated in 96-well, flat-bottomed plates (1×104 cells/100 μL/well) in F-12K media containing 0.5% heat-inactivated FBS and cultured at 37 ℃ for 24 h to quiesce the cells. Serial dilutions of compounds prepared in medium containing 1% DMSO are then added for 2 h, followed by the addition of mitogenic concentrations of either VEGF at 5 ng/mL or 20 ng/mL or acidic fibroblast growth factor at 0.25–5 ng/mL in media. The final concentration of DMSO in the assay is 0.25%. After 24 h, either [3H]thymidine (1 μCi/well) or BrdUrd is added, and the cell monolayers are incubated for another 24 h. The uptake of either [3H]thymidine or BrdUrd into cells is quantitated using a liquid scintillation counter or a BrdUrd ELISA, respectively.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Biochemical kinase assays: Solubilized membranes from 3T3 Flk-1 cells are added to polystyrene ELISA plates that had been precoated with a monoclonal antibody that recognizes Flk-1. After an overnight incubation with lysate at 4 ℃, serial dilutions of SU5416 are added to the immunolocalized receptor. To induce autophosphorylation of the receptor, various concentrations of ATP are added to the ELISA plate wells containing serially diluted solutions of SU5416. The autophosphorylation is allowed to proceed for 60 min at room temperature and then stopped with EDTA. The amount of phosphotyrosine present on the Flk-1 receptors in the individual wells is determined by incubating the immunolocalized receptor with a biotinylated monoclonal antibody directed against phosphotyrosine. After removal of the unbound anti-phosphotyrosine antibody, avidin-conjugated horseradish pero-idase H is added to the wells. A stabilized form of 3,3 9,5,5 9-tetramethyl benzidine dihydrochloride and Water2 is added to the wells. The color readout of the assay is allowed to develop for 30 min, and the reaction is stopped with H2SO4. |
| 體外活性 | 在10種測試腫瘤細(xì)胞系中,Semaxanib對(duì)其中8種(A431,Calu-6,C6,LNCAP,EPH4-VEGF,3T3HER2,488 g2M2以及SF763T細(xì)胞)的皮下生長均有明顯抑制作用,平均死亡率為2.5%.Semaxanib劑量依賴性抑制體內(nèi)A375腫瘤的生長.Semaxanib（25 mg/kg/day）具有較強(qiáng)抗血管生成活性,顯著降低腫瘤微血管系統(tǒng)的總功能性血管密度.Semaxanib（i.p.）可抑制>85%的皮下腫瘤生長,且無可檢測的毒性. |
| 體內(nèi)活性 | Semaxanib劑量依賴性抑制VEGF（IC50：0.04 μM）和FGF（IC50：50 μM）誘導(dǎo)的有絲分裂。Semaxanib不影響C6膠質(zhì)瘤,Calu 6肺癌,A375黑素瘤,A431 鱗狀細(xì)胞癌,和SF767T 神經(jīng)膠質(zhì)瘤細(xì)胞在體外的生長（IC50s>20 μM）。在Flk-1過表達(dá)的NIH 3T3細(xì)胞中,Semaxanib對(duì)Flk-1受體的VEGF-依賴性磷酸化具有抑制作用（IC50：1.04 μM）。Semaxanib可抑制NIH 3T3細(xì)胞中PDGF依賴性自身磷酸化（IC50：20.3 μM）。 |
| 存儲(chǔ)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)
DMSO : 7.14 mg/mL (29.98 mM), Sonication is recommended.
Ethanol : 2 mg/mL (8.39 mM)
|
| 關(guān)鍵字 | (Z) Semaxinib | (Z)-Semaxanib | (Z)-SU5416 | TAMH cells | c-Met/HGFR | (Z)Semaxinib | Semaxinib | inhibit | Inhibitor | SU-5416 | SU 5416 | HepG2 cells | cytotoxicity |
| 相關(guān)產(chǎn)品 | Ribociclib | Lenvatinib | Axitinib | Sorafenib tosylate | Lenvatinib mesylate | Sanguinarine chloride | Regorafenib | Pazopanib | Nintedanib | Sorafenib | Regorafenib monohydrate | Taxifolin |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 抗癌活性化合物庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |