| 名稱 | Galunisertib |
| 描述 | Galunisertib (LY2157299) is a TGF-β receptor type I (TGF-βRI) inhibitor (IC50=56 nM) that is selective. Galunisertib has antitumor activity and can be used in combination with PD-1 inhibitors. |
| 細(xì)胞實(shí)驗(yàn) | Cell survival was determined using the MTT assay. The conversion of yellow water-soluble tetrazolium MTT into purple insoluble formazan is catalyzed by mitochondrial dehydrogenases and used to estimate the number of viable cells. In brief, cells were seeded in 96-well tissue culture plates at a density of 2 × 103 cells/well. After drug exposure, cells were incubated with 0.4 mg/mL MTT for 4 hours at 37°C. After incubation, the supernatant was discarded, insoluble formazan precipitates were dissolved in 0.1 mL of DMSO, and the absorbance was measured at 560 nm by use of a microplate reader. Wells with untreated cells or with drug-containing medium without cells were used as positive and negative controls respectively. For proliferation assay, MTT assay was done daily to determine the number of viable cells in untreated control and galunisertib-treated group [2]. |
| 激酶實(shí)驗(yàn) | Briefly, the assay was first done at 30°C for 4 h in a 96-well plate containing 2 ng/mL TGF-bR KD, 100 mM Hepes pH 7.5, 4 mM MgCl2, 0.2 mM MnCl2, 0.4 mM sodium orthovanadate, 2 mM DL-dithiothreitol, and 10mM ATP. After incubation, 50mL of Kinase-Glo plus reagent was added and further incubated at 25°C for 30 min. Subsequently, a 100mL aliquot of each reaction mixture was transferred to a black mictotiter plate and the luminescence was measured by a vector counter. The inhibitory activity IC50 was tested in duplicate for each sample [1]. |
| 動(dòng)物實(shí)驗(yàn) | Transgenic mice expressing a fusion gene (Alb/TGF) consisting of modified porcine TGF-β1 cDNA under the control of the regulatory elements of the mouse albumin gene (26) were used under animal institute approved protocol. Mice were given LY-2157299 at a dose of 100mg/kg/day in NaCMC/SLS/PVP/antifoam solution by gastric lavage using a curved 14 G needle. Blood counts were analyzed by the Advia machine. Mice femurs were flushed and bone marrows cells were used for clonogenic assays [3]. |
| 體外活性 | 方法: 小鼠胚胎成纖維細(xì)胞 NIH3T3 用 Berzosertib (0.0001-10 μM) 處理 2 h，隨后用 TGFβ1 孵育過夜，使用 3H-thymidine proliferation assay 檢測細(xì)胞增殖。
結(jié)果: Berzosertib 抑制 TGFβ1 誘導(dǎo)的增殖，IC50 為 0.396 μM。[1]
方法: 七種 HCC 細(xì)胞系 JHH6、SK-HEP1、SK-Suni、SK-Sora、HepG2、Hep3B、HuH7 用 Galunisertib (1-10 μM) 和 TGF-β (5 ng/mL) 處理 5-24 h，使用 Western Blot 檢測靶點(diǎn)蛋白表達(dá)水平。
結(jié)果: 添加 Galunisertib 以劑量和時(shí)間依賴的方式降低了所有細(xì)胞系中 p-Smad2 的表達(dá)水平，與 TGF-β 誘導(dǎo)無關(guān)。[2] |
| 體內(nèi)活性 | 方法: 為檢測體內(nèi)抗腫瘤活性，用 Galunisertib (75 mg/kg，10% beta-cyclodextrin-HCl) 灌胃給藥攜帶 MX1、Calu6 或 4T1 腫瘤的 athymic nu/nu 小鼠，每天兩次，持續(xù) 20-40 天。
結(jié)果: Galunisterib 單藥治療都導(dǎo)致了明顯的腫瘤生長延遲。對于MX1，Galunisertib 治療導(dǎo)致腫瘤生長延遲 10.3±4.3天。對于 Calu6，Galunisertib 治療導(dǎo)致腫瘤生長推遲 8.3±2.6天。對于 4T1，Galunisertib 治療導(dǎo)致腫瘤生長延遲 13±2.4天。[1] |
| 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 | DMSO : 50 mg/mL (135.35 mM)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 6.9 mg/mL (18.68 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
Ethanol : Insoluble
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| 關(guān)鍵字 | inhibit | LY 2157299 | Transforming growth factor beta receptors | Inhibitor | LY-2157299 | TGF-β Receptor | Galunisertib |
| 相關(guān)產(chǎn)品 | Monocrotaline | Pirfenidone | A 83-01 | Halofuginone | Chromenone 1 | LY-364947 | BMP signaling agonist sb4 | SB-431542 | Alantolactone | LDN-193189 2HCl | Hydrochlorothiazide | Asiaticoside |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 抗癌活性化合物庫 | 已知活性化合物庫 | 激酶抑制劑庫 | TGF-β/Smad靶點(diǎn)化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 表型篩選靶點(diǎn)鑒定庫 | 抗癌藥物庫 |