Pazopanib
作者：齊岳
發(fā)布時(shí)間：2023-08-25
08:58:38
點(diǎn)擊數(shù)：
產(chǎn)品名稱：Pazopanib
產(chǎn)品描述：
| 產(chǎn)品描述 | Pazopanib, a small molecule inhibitor, inhibits multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits VEGFR-1, -2 and -3, c-kit and PDGF-R, which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated. |
| 靶點(diǎn)活性 | c-Kit:74 nM, PDGFR:84 nM, VEGFR1:10 nM, VEGFR3:47 nM, VEGFR2:30 nM |
| 體外活性 | 小鼠對(duì)Pazopanib**具有良好的耐受性,且每組小鼠的體重未出現(xiàn)差異.與低劑量組（載體或10 mg/kg Pazopanib）小鼠相比,高劑量組（30 mg/kg或100 mg/kg Pazopanib）小鼠負(fù)荷明顯降低. |
| 體內(nèi)活性 | 在包括SYO-1和HS-SY-II細(xì)胞的所有滑膜肉瘤細(xì)胞系中,Pazopanib均呈現(xiàn)劑量生長(zhǎng)依賴的抑制作用。Pazopanib濃度為1μg/ml時(shí),SYO-1和HS-SY-II細(xì)胞的增殖被抑制,濃度為5μ時(shí)被完全抑制。在VEGF誘導(dǎo)的HUVEC 細(xì)胞中,Pazopanib能有效抑制VEGFR2磷酸化作用（IC50：8 nM）。Pazopanib由于引起G1期阻滯從而抑制滑膜肉瘤細(xì)胞生長(zhǎng)。和載體處理的細(xì)胞不同,經(jīng)Pazopanib處理的SYO-1細(xì)胞中的Akts,GSK-3β,JNKs,p70 S6 激酶,和mTOR磷酸化作用受到抑制。濃度在20 mg/ml和22.5 mg/ml之間時(shí),Pazopanib濃度逐漸增加,RPE細(xì)胞活性降低。 |
| 激酶實(shí)驗(yàn) | 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 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (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 compound 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[1]. |
| 細(xì)胞實(shí)驗(yàn) | Pazopanib is prepared in DMSO and then diluted to final concentration in medium[1]. The effect of Pazopanib on cell proliferation is measured using 5-bromo-2-deoxyuridine (BrdU) incorporation method using commercially available kits. HUVEC is seeded in medium containing 5% fetal bovine serum (FBS) in type 1 collagen coated 96-well plates and incubated overnight at 37°C, 5% CO2. The medium is aspirated from the cells, and various concentrations of Pazopanib in serum-free medium are added to each well. After 30 min, either VEGF (10 ng/mL) or bFGF (0.3 ng/mL) is added to the wells. Cells are incubated for an additional 72 h and BrdU (10 μM) is added during the last 18 to 24 h of incubation. At the end of incubation, BrdU incorporation in cells is measured by ELISA. Data are fitted with a curve described by the equation, y=Vmax(1?(x/(K+x))), where K is equal to the IC50[1]. |
| 別名 | GW786034, 帕唑帕尼 |
| 分子量 | 437.52 |
| 分子式 | C21H23N7O2S |
| CAS No. | 444731-52-6 |
存儲(chǔ)
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
Ethanol: <1 mg/mL
H2O: <1 mg/mL
DMSO: 81 mg/mL (185.1 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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