| 名稱 | GW788388 |
| 描述 | GW788388 is a potent and selective inhibitor of ALK5, also inhibits TGF-(beta) type II receptor and activin type II receptor activities. |
| 細(xì)胞實(shí)驗(yàn) | Cell viability/proliferation assays are done according to the manufactures instructions (CellTiter 96 Aqueous One Solution Cell Proliferation Assay). Viability and proliferation are measured after 72 hours GW788388 treatment in the presence or absence of TGF-β.(Only for Reference) |
| 激酶實(shí)驗(yàn) | ALK5 Fluorescence Polarization Binding Assay: GW788388 binding to ALK5 is tested on purified recombinant GST?ALK5 (residues 198-503). Displacement of rhodamine green fluorescently labeled ATP competitive inhibitor by different concentrations of GW788388 is used to calculate a binding pIC50. GST?ALK5 is added to a buffer containing 62.5 mM N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (Hepes), pH 7.5, 1 mM dithiothreitol (DTT), 12.5 mM MgCl2, 1.25 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS), and 1 nM rhodamine green-labeled ligand so that the final ALK5 concentration is 10 nM based on active-site titration of the enzyme. The enzyme/ligand reagent (40 μL) is added to 384-well assay plates containing 1 μL of different concentrations of GW788388. The plates are read immediately on a LJL Acquest fluorescence reader with excitation, emission, and dichroic filters of 485, 530, and 505 nm, respectively. The fluorescence polarization for each well is calculated by the Acquest and is then imported into curve-fitting software for construction of concentration?response curves. |
| 體外活性 | 在嘌呤霉素氨基核甙誘導(dǎo)的腎臟纖維化模型中,GW788388（10 mg/kg）能夠誘導(dǎo)膠原A1 mRNA 表達(dá).在患晚期糖尿病腎病鼠中,GW788388通過減少TGF-β 信號(hào),降低纖維反應(yīng).在心肌梗塞鼠中,GW788388處理后,能夠明顯抑制收縮功能,降低心肌細(xì)胞肥大 ,且降低激活的Smad2, α-SMA. |
| 體內(nèi)活性 | GW788388能夠抑制ALK5, ALK4, ALK7 和TGF-β調(diào)節(jié)的生長。在細(xì)胞實(shí)驗(yàn)中（IC50=93 nM）,GW788388具有抗TGF-β誘導(dǎo)的Smad激活,且抑制靶點(diǎn)基因表達(dá)。 |
| 存儲(chǔ)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 : 1 mg/mL (2.35 mM), Sonication is recommended.
DMSO : 10 mg/mL (23.5 mM), Sonication is recommended.
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| 關(guān)鍵字 | Transforming growth factor beta receptors | TGF-β/Smad | TGF-β Receptor | TGFβ | TGFbeta/Smad | TGF-beta | TGFbeta | TGF-b/Smad | TGFb | Smad | Inhibitor | inhibit | GW-788388 | GW788388 | ALK5 |
| 相關(guān)產(chǎn)品 | Trimethylamine N-oxide | Pirfenidone | Crizotinib | Melamine | A 83-01 | SB-431542 | Alectinib | Cetrimonium bromide | Galunisertib | Alantolactone | Brigatinib | Hydrochlorothiazide |
| 相關(guān)庫 | 抑制劑庫 | 抗乳腺癌化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 抗胰腺癌化合物庫 | 激酶抑制劑庫 | HIF-1化合物庫 | 抗肥胖化合物庫 | TGF-β/Smad靶點(diǎn)化合物庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 | 細(xì)胞重編程化合物庫 |