| 名稱 | AG490 |
| 描述 | AG490 (Tyrphostin B42) is an inhibitor of EGFR (IC50: 0.1 μM). It is 135-fold more selective for EGFR than ErbB2, also inhibits JAK2 with no effect to Lyn, Lck, Syk, Btk, and Src. |
| 細(xì)胞實(shí)驗(yàn) | Cells are exposed to different concentrations of AG-490 for 16 hours. For the determination of cell proliferation, [3H]tymidine (1 μCi) is added 6 hours or more before the cultures are terminated. Cells are then collected and samples counted in a liquid scintillation counter. (Only for Reference) |
| 激酶實(shí)驗(yàn) | In vitro kinase autophosphorylation: AG-490 is dissolved in DMSO 10%-Water-ethanol 45%. Crude membrane extracts (0.125 μg/mL) are preactivated with EGF (20 nM) in 50 mM HEPES buffer, pH 7.6, and 125 mM NaCl, for 15 minutes at 4 °C. Autophosphorylation activity of EGFR or ErbB2 kinase is assayed at 4 °C for 30 seconds in V-shaped 96-well plates. Membrane extracts (8 μL) are added to each well containing reaction mixture (12 μL, 50 mM, HEPES, pH 7.4,125 mM NaCl, 12 mM M8Ac2, 2 mM MnCl2, 1 mM NaVO3, 1 μM ATP, and 1 μCi[γ-32P]ATP, final concentrations) and increasing concentrations of AG-490 (4 μL). After termination by addition of hot sample buffer, the samples are run on a 6% SDS-polyacrylamide gel electrophoresis minigel, the gels dried, and autoradiography performed during the linear exposure time period. The receptor bands are scanned densitrometrically, and the results analyzed by the Ez-Fit program. For the analysis of autophosphorylation of JAK2, JAK2 is immunoprecipitated by using anti-JAK2 antibody from lysates of G2 cells pretreated for 16 hours with increasing concentrations of AG-490 (0-50 μM). Immune complexes are then immunoblotted with anti-phosphotyrosine antibody. A dose-dependent inhibition of in vitro kinase activity is demonstrated by assessing JAK2 autophosphorylation. |
| 體外活性 | 在體內(nèi),AG-490處理可促使小鼠骨髓瘤細(xì)胞凋亡,但不影響IL-12誘導(dǎo)的巨噬細(xì)胞活化和IFN-γ產(chǎn)量.AG-490（0.5 mg/day）處理裸鼠10天,對(duì)JAK2 V617F突變誘導(dǎo)的腫瘤形成及入侵有顯著抑制效果.AG-490可大幅降低CD45+和HLA-DR+細(xì)胞數(shù),在骨髓中,其可使上述細(xì)胞數(shù)分別從48% 和46%降低到不可檢測(cè)水平,這未處理小鼠脾臟中,則從38%和 22% 降低到不可檢測(cè)水平. |
| 體內(nèi)活性 | 通過誘導(dǎo)程序性細(xì)胞死亡,AG-490（5 μM）幾乎完全抑制所有ALL 細(xì)胞生長(zhǎng),而不影響正常造血功能。AG-490（30 μM）既對(duì)Epo誘導(dǎo)的野生型JAK2磷酸化有抑制作用,也對(duì)組成型的JAK2 V617F突變型磷酸化有抑制作用。AG-490（50 μM）對(duì)表達(dá)Bcr-Abl 突變型E255K和T315I的抗Imatinib的BaF3細(xì)胞凋亡具有誘導(dǎo)作用。AG-490（60-100 μM）對(duì)Stat3sm組成型激活有抑制作用,且抑制自發(fā)的（IC50：75 μM）或IL-2誘導(dǎo)的（IC50：20 μM）蕈菌腫瘤細(xì)胞生長(zhǎng)。AG-490（100 μM）抑制Akt磷酸化和核因子-κB激活,且激活GSK-3β并導(dǎo)致c-Myc降低。AG-490對(duì)EGF依賴的HER 14細(xì)胞增殖有抑制作用（IC50：3.5 μM）。通過對(duì)JAK3和 STAT5a/b活性的抑制,AG-490有效抑制IL-2調(diào)節(jié)的人T細(xì)胞生長(zhǎng)（IC50：25 μM）。 盡管AG-490 （5 μM）單獨(dú)給藥不影響FDrv210H細(xì)胞增殖,但其可協(xié)同增強(qiáng)STI571對(duì)p210bcr-abl的抑制從而促進(jìn)增殖效果。 |
| 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 : 40 mg/mL (135.92 mM)
Ethanol : 6 mg/mL (20.38 mM)
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| 關(guān)鍵字 | Tyrphostin AG490 | Epidermal growth factor receptor | Inhibitor | Tyrphostin B-42 | ErbB-1 | STAT | Janus kinase | Autophagy | Tyrphostin B 42 | EGFR | HER1 | Tyrphostin AG-490 | inhibit | JAK | AG490 |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Gefitinib | Aceglutamide | Hydroxychloroquine | Curcumin | Stavudine | Salicylic acid | Paeonol | Sodium 4-phenylbutyrate |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 抗癌活性化合物庫(kù) | 已知活性化合物庫(kù) | 激酶抑制劑庫(kù) | JAK-STAT 化合物庫(kù) | 抗衰老化合物庫(kù) | 干細(xì)胞分化化合物庫(kù) | 膜蛋白靶向化合物庫(kù) | 酪氨酸激酶分子庫(kù) |