| 名稱 | Vatalanib dihydrochloride |
| 描述 | Vatalanib dihydrochloride (PTK787 dihydrochloride)(IC50=37 nM) is an inhibitor of VEGFR2/KDR. It exhibits less effective against VEGFR1/Flt-1 and 18-fold against VEGFR3/Flt-4. |
| 細(xì)胞實(shí)驗(yàn) | As a test of the ability of PTK787/ZK 222584 to inhibit a functional response to VEGF, an endothelial cell proliferation assay, based on BrdUrd incorporation is used. Subconfluent HUVECs are seeded into 96-well plates coated with 1.5% gelatin and then incubated at 37 °C and 5% CO2 in growth medium. After 24 hours, growth medium is replaced by basal medium containing 1.5% FCS and a constant concentration of VEGF (50 ng/mL), bFGF (0.5 ng/mL), or FCS (5%), in the presence or absence of PTK787/ZK 222584. As a control, wells without growth factor are also included. After 24 hours of incubation, BrdUrd labeling solution is added, and cells incubated an additional 24 hours before fixation, blocking, and addition of peroxidase-labeled anti-BrdUrd antibody. Bound antibody is then detected using 3,3′5,5′-tetramethylbenzidine substrate, which results in a colored reaction product that is quantified spectrophotometrically at 450 nm. (Only for Reference) |
| 激酶實(shí)驗(yàn) | VEGF Receptor Tyrosine Kinase Assays : The in vitro kinase assays are performed in 96-well plates as a filter binding assay, using the recombinant GST-fused kinase domains expressed in baculovirus and purified over glutathione-Sepharose. γ-[33P]ATP is used as the phosphate donor, and poly-(Glu:Tyr 4:1) peptide is used as the acceptor. Recombinant GST-fusion proteins are diluted in 20 mM Tris·HCl (pH 7.5) containing 1–3 mM MnCl2, 3–10 mM MgCl2, 0.25 mg/mL polyethylene glycol 20000, and 1 mM DTT, according to their specific activity. Each GST-fused kinase is incubated under optimized buffer conditions [20 mM Tris-HCl buffer (pH 7.5), 1–3 mM MnCl2, 3–10 mM MgCl2, 3–8 μg/mL poly-(Glu:Tyr 4:1), 0.25 mg/mL polyethylene glycol 20000, 8 μM ATP, 10 μM sodium vanadate, 1 mM DTT, and 0.2 μCi[γ-33P]ATP in a total volume of 30 μL in the presence or absence of a test substance for 10 minutes at ambient temperature. The reaction is stopped by adding 10 μL of 250 mM EDTA. Using a 96-well filter system, half the volume (20 μL) is transferred onto a Immobilon-polyvinylidene difluoride membrane. The membrane is then washed extensively in 0.5% H3PO4 and then soaked in ethanol. After drying, Microscint cocktail is added, and scintillation counting is performed. IC50s for PTK787/ZK 222584 or SU5416 in these as well as all assays described below are calculated by linear regression analysis of the percentage inhibition. |
| 體外活性 | Vatalanib對(duì)Flk、c-Kit和PDGFRβ的抑制作用分別表現(xiàn)在IC50為270 nM、730 nM和580 nM。此外，通過(guò)抑制VEGF在HUVECs中誘導(dǎo)的胸腺嘧啶核苷酸的結(jié)合，Vatalanib展現(xiàn)了IC50為7.1 nM的抗增殖效果，并且在相同的劑量范圍內(nèi)，劑量依賴性抑制VEGF誘導(dǎo)的內(nèi)皮細(xì)胞的存活和遷移，而對(duì)不表達(dá)VEGF受體的細(xì)胞沒(méi)有細(xì)胞毒性或抗增殖作用。[1] 最近的研究表明，Vatalanib顯著抑制肝細(xì)胞性癌細(xì)胞的生長(zhǎng)，并通過(guò)增加Bax蛋白水平和降低Bcl-xL與Bcl-2，增強(qiáng)了IFN/5-FU誘導(dǎo)的細(xì)胞凋亡。[2] |
| 體內(nèi)活性 | Vatalanib 通過(guò)每日一次口服（25-100 mg/kg）在生長(zhǎng)因子植入模型和腫瘤細(xì)胞驅(qū)動(dòng)的血管生成模型中對(duì) VEGF 和 PDGF 的血管生成反應(yīng)產(chǎn)生劑量依賴性抑制。在相同劑量范圍內(nèi)，Vatalanib 還能抑制裸鼠體內(nèi)多種人類癌癥的生長(zhǎng)和轉(zhuǎn)移，而對(duì)循環(huán)血細(xì)胞或骨髓白細(xì)胞無(wú)顯著影響。[1] |
| 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 | DMSO : 79 mg/mL (188.2 mM)
H2O : 10 mg/mL (23.82 mM)
Ethanol : 6 mg/mL (14.29 mM)
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| 關(guān)鍵字 | Inhibitor | Vascular endothelial growth factor receptor | CGP-79787 | VEGFR | CGP-797870 | Vatalanib | PTK787 Dihydrochloride | ZK222584 | PTK 787 Dihydrochloride | PTK-787 Dihydrochloride | Apoptosis | CGP797870 | PTK-787 | CGP 797870 Dihydrochloride | Vatalanib dihydrochloride | CGP79787 Dihydrochloride | ZK-222584 | ZK 222584 | ZK 222584 Dihydrochloride | CGP 79787 | ZK-222584 Dihydrochloride | PTK 787 | CGP 79787 Dihydrochloride | CGP797870 Dihydrochloride | CGP 797870 | CGP-797870 Dihydrochloride | ZK222584 Dihydrochloride | PTK787 | Vatalanib (PTK787) | inhibit | CGP-79787 Dihydrochloride | Vatalanib Dihydrochloride | CGP79787 |
| 相關(guān)產(chǎn)品 | L-Glutamic acid | Metronidazole | 5-Fluorouracil | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
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