| 名稱 | Maraviroc |
| 描述 | Maraviroc (UK-427857, Selzentry) belongs to small molecule drugs and is a C-C chemokine receptor 5 antagonist with oral activity and selectivity. This compound is used for the treatment of HIV-1 infection and has also shown anti-inflammatory, neuroprotective, and potential antitumor synergistic effects in research. |
| 細胞實驗 | Drug susceptibility assays are performed in 24-well tissue culture plates. Duplicate eight-point dilution series of Maraviroc are prepared in DMSO and medium to yield a final DMSO concentration of 0.1% (vol/vol) in the assay. PHA-stimulated PBMC or PM-1 cells are infected with virus for 1 hour at 37 °C. Cells are subsequently washed once, and 3.6 × 105 PBMC or 2.0 × 105 PM-1 cells are added to each well of assay plates containing diluted Maraviroc. Plates are incubated for 5 days (lab-adapted strains) or 7 days (primary isolates) at 37 °C in a humidified 5% CO2 (vol/vol) atmosphere.(Only for Reference) |
| 激酶實驗 | Inhibition of chemokine binding to CCR5: Binding of 125I-labeled MIP-1α, MIP-1β, and RANTES to CCR5 is measured using intact HEK-293 cells stably expressing the receptor or membrane preparations thereof. Briefly, cells are resuspended in binding buffer (50 mM HEPES containing 1 mM CaCl2, 5 mM MgCl2, and 0.5% bovine serum albumin [BSA] and adjusted to pH 7.4) to a density of 2 × 106 cells/ml. For membrane preparations, phosphate-buffered saline (PBS)-washed cells are resuspended in lysis buffer (20 mM HEPES, 1 mM CaCl2, 1 tablet COMPLETE per 50 mL, pH 7.4) prior to homogenization in a Polytron hand-held homogenizer, ultracentrifugation (40,000× g for 30 min), and resuspension in binding buffer to a protein concentration of 0.25 mg/mL (12.5 μg of membrane protein is used in each well of a 96-well plate). 125I-radiolabeled MIP-1α, MIP-1β, and RANTES are prepared and diluted in binding buffer to a final concentration of 400 pM in the assay. Maraviroc dilutions are added to each well to a final volume of 100 μL, the assay plates incubate for 1 hour, and the contents filter through preblocked and washed Unifilter plates which are counted following overnight drying. |
| 體外活性 | 方法：采用TZM-bl細胞，將系列稀釋的Maraviroc與HIV-1 Ba-L毒株共孵育48小時，通過熒光素酶法檢測。
結(jié)果：Maraviroc的EC50值為0.015 μM，對CXCR4嗜性毒株無活性，表明其具有特異性CCR5拮抗作用。[1] |
| 體內(nèi)活性 | 方法：采用人源化NOD/scid-IL-2Rγc null小鼠模型，腹腔注射HIV-1ADA建立感染，Maraviroc以120 mg/kg劑量腹腔注射，每日兩次，持續(xù)3周，溶劑為DMSO:PBS混合液。
結(jié)果：Maraviroc顯著降低血和腦組織病毒載量，減輕免疫抑制，減少腦內(nèi)Aβ生成和Tau蛋白磷酸化，保護血腦屏障和神經(jīng)元。[2] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 255 mg/mL (496.43 mM), Sonication is recommended.
Ethanol : 51.4 mg/mL (100.06 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 5 mg/mL (9.73 mM), Sonication is recommended.
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| 關(guān)鍵字 | UK427857 | UK 427857 | RANTES | MIP-1β | MIP-1α | Maraviroc | Inhibitor | inhibit | Human immunodeficiency virus | HIVProtease | HIV Protease | HIV | CCR | CC chemokine receptor |
| 相關(guān)產(chǎn)品 | Tenofovir | Valproic Acid | Pirfenidone | (-)-Epigallocatechin Gallate | Emtricitabine | Dolutegravir intermediate-1 | Dextran sulfate sodium salt (MW 5000) | Lamivudine | 5-Fluorouracil | Decanedioic acid | Stavudine | Dimethyl fumarate |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 臨床失敗化合物庫 | EMA 上市藥物庫 | FDA 上市藥物庫 | 抗病毒庫 | GPCR靶點分子庫 | 神經(jīng)退行性疾病化合物庫 | 膜蛋白靶向化合物庫 | 免疫/炎癥分子化合物庫 | 藥物功能重定位化合物庫 |