| 名稱 | GSK429286A |
| 描述 | GSK429286A (RHO-15) is a specific inhibitor of ROCK1/2 (IC50: 14/63 nM). |
| 激酶實(shí)驗(yàn) | Binding affinity assays: TR-FRET-binding affinity assays are performed for BCL-2, BCL-XL, and MCL-1 in 4.52?mM monobasic potassium phosphate, 15.48?mM dibasic potassium phosphate, 1?mM sodium EDTA, 0.05% Pluronic F-68 detergent, 50?mM sodium chloride, and 1?mM DTT (pH 7.5). For MCL-1 assays, GST-tagged MCL-1 (1?nM) is mixed with 100?nM f-Bak, 1?nM Tb-labeled anti-GST antibody, and compound at room temperature (RT) for 60?min. Fluorescence is measured on an Envision plate reader using a 340/35?nm excitation filter and 520/525 (f-Bak) and 495/510?nm (Tb-labeled anti-GST antibody) emission filters. |
| 體外活性 | GSK429286A（3-30 mg/kg,p.o.）劑量依賴性顯著降低自發(fā)性高血壓大鼠的平均動脈壓, GSK429286A（30 mg/kg）處理約2 h后,最大降低50 mmHg.在雄性Sprague-Dawley大鼠體內(nèi),GSK429286A的口服生物利用度為61%. |
| 體內(nèi)活性 | GSK429286A（1 μM）可使ROCK2活性降低20倍,該濃度下僅有MSK1的活性降低了約5倍。與ROCK常用抑制劑Y-27632相比,GSK429286A是選擇性更高的ROCK2抑制劑,即使30 μM對LRRK2也無明顯抑制,IC50比對ROCK2的高500倍。與GSK269962A相同,在HEK-293細(xì)胞中,GSK429286A（10 μM）可消除基底或G14V-Rho突變體誘導(dǎo)的MYPT Thr850上的磷酸化作用,效果與H-1152和Y-27632相似,與ROCK介導(dǎo)的磷酸化一致,G14V-Rho是否存在,GSK429286A均不影響ERM蛋白磷酸化。GSK429286A對RSK（IC50：0.78 μM）和p70S6K（IC50：1.94 μM）也有輕度抑制。GSK429286A對大鼠主動脈環(huán)擴(kuò)張有顯著抑制（IC50：190 nM）。 |
| 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 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 10 mg/mL (23.13 mM), Solution.
Ethanol : 4 mg/mL (9.25 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+90% Saline : < 10 mg/mL (23.13 mM), Lower concentrations may be soluble, but exact solubility limit is unknown.
DMSO : 140 mg/mL (323.8 mM), Sonication is recommended.
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| 關(guān)鍵字 | ROK | ROCK2 | ROCK1 | ROCK | Rho-kinase | Rho-associated protein kinase | Rho-associated kinase | RHO15 | RHO 15 | Inhibitor | inhibit | GSK-429286A | GSK429286A |
| 相關(guān)產(chǎn)品 | Y-27632 dihydrochloride | ITX3 | Fasudil hydrochloride | ROCK-IN-5 | Fasudil | Tofacitinib | CAY10746 | Y-27632 | RKI-1447 | SAR407899 hydrochloride | Thiazovivin | GSK180736A |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 神經(jīng)再生化合物庫 | 含氟化合物庫 | 高選擇性抑制劑庫 | 細(xì)胞骨架化合物庫 | TGF-β/Smad靶點(diǎn)化合物庫 | 膜蛋白靶向化合物庫 | 抗代謝疾病化合物庫 | 細(xì)胞重編程化合物庫 |