| 名稱 | Palomid 529 |
| 描述 | Palomid 529 (SG 00529) has been used in trials studying the treatment of Age-Related Macular Degeneration. |
| 細(xì)胞實(shí)驗(yàn) | Human umbilical vascular endothelial cells (HUVEC) are used. The proliferation assay is carried out by seeding the HUVECs in 96-well plates at a density of 1,000 per well in complete medium. Following a 24-hour plating period, the cells are starved for 24 hours in 0.5% serum before being treated with Palomid 529 in the presence of 10 ng/mL basic fibroblast growth factor (bFGF) or VEGF in complete medium. After 48 hours, cell number is determined using a colorimetric method. The results are expressed as the percentage of the maximal bFGF or VEGF response in the absence of Palomid 529. Nonproliferating endothelial cells are assayed by growing HUVECs to quiescence in 96-well plates and treating with Palomid 529 for 48 hours. Initially, 5,000 cells per well are seeded and confluence is achieved the next day. The plates are incubated for another 24 hours to ensure growth arrest before treatment with Palomid 529. (Only for Reference) |
| 激酶實(shí)驗(yàn) | Estrogen receptor binding assays: The proteins are produced with rabbit reticulocyte lysates. The amount of template used in each reaction is determined empirically and expression is monitored in parallel reactions where [35S]methionine is incorporated into the receptor followed by gel electrophoresis and exposure to film. Binding reactions of the estrogen receptors (ER) and Palomid 529 are carried out in 100 mL final volumes in TEG buffer [10 mM Tris (pH 7.5), 1.5 mM EDTA, 10% glycerol]. In vitro transcribed-translated receptor (5 μL) is used in each binding reaction in the presence of 0.5 nM [3H]estradiol (E2). Palomid 529 is routinely tested from 10?11 to 10?6 M and diluted in ethanol. The reactions are incubated at 4 °C overnight and bound E2 is quantified by adding 200 mL dextran-coated charcoal. After a 15-minutes rotation at 4 °C, the tubes are centrifuged for 10 minutes and 150 mL of the supernatant are added to 5 mL scintillation mixture for determination of cpm by liquid scintillation counting. The maximum binding is determined by competing bound E2 with only the ethanol vehicle. Controls for background are included in each experiment using 5 mL unprogrammed rabbit reticulocyte lysate. This value, typically 10% to 15% of the maximal counts, is subtracted from all values. The data are plotted and Ki values are calculated. Experiments are conducted at least thrice in duplicate. |
| 體外活性 | Palomid 529抑制腫瘤生長,血管生成和血管通透性.在兔視網(wǎng)膜脫離模型中,Palomid 529可有效抑制Müller細(xì)胞增殖,神經(jīng)膠質(zhì)瘢痕形成和感光細(xì)胞死亡.Palomid 529劑量依賴性抑制Ad-VEGF-A驅(qū)動(dòng)的血管生成,裸鼠灌胃Palomid 529可抑制C6V10膠質(zhì)瘤生長.與對照組相比,Palomid 529處理PC-3腫瘤小鼠可減少57.1%的腫瘤生長.Palomid 529明顯抑制小鼠Brca1缺失腫瘤生長模型中Akt和 mTOR信號通路. |
| 體內(nèi)活性 | Palomid529不僅降低缺血性視網(wǎng)膜的增殖,而且能改善血管形成的組織和結(jié)構(gòu)。Palomid 529抑制VEGF介導(dǎo)和bFGF介導(dǎo)的內(nèi)皮細(xì)胞增殖,IC 50分別為20 nM 和30 nM。Palomid 529可誘導(dǎo)內(nèi)皮細(xì)胞凋亡,降低血管內(nèi)皮生長因子VEGF-A誘導(dǎo)的pAktS473,pGSK3βS9和pS6磷酸化。在肺癌NCI- 60細(xì)胞系中,Palomid 529顯示高效的抗增殖活性,GI50< 35 μM。此外,Palomid 529可顯著增強(qiáng)輻射對前列腺癌細(xì)胞（PC-3）的抗增殖作用。Palomid 529對PC-3細(xì)胞產(chǎn)生濃度依賴性生長抑制。Palomid 529抑制PC-3中輻射誘導(dǎo)的p-Akt激活,并降低Bcl-2/Bax的比例。 |
| 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 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 50 mg/mL (123.02 mM), Sonication is recommended.
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| 關(guān)鍵字 | mTOR | Apoptosis | P-529 | Palomid-529 | Inhibitor | Palomid529 | P 529 | SG00529 | Mammalian target of Rapamycin | Palomid 529 | SG-00529 | inhibit |
| 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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