| 名稱 | ADH-1 |
| 描述 | ADH-1 (Exherin) is an N-cadherin antagonist, inhibits N-cadherin mediated cell adhesion with potential antineoplastic and antiangiogenic activities. |
| 激酶實(shí)驗(yàn) | Kinase Activity Assays: The effect of VX-509 on JAK3 activity is assessed by measuring the residual kinase activity of the recombinantly expressed JAK3 kinase domain using a radiometric assay. The final concentrations of the components in the assay are as follows: 100 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM dithiothreitol (DTT), 0.01% BSA, 0.25 nM JAK3, 0.25 mg/ml polyE4Y, and 5 μM 33P-γ-ATP (200 μCi/μMol). A 10 mM stock solution of VX-509 is prepared in DMSO, from which additional dilutions are prepared. A substrate mixture (100 mM HEPES, 10 mM MgCl2, 0.5 mg/ml polyE4Y, and 10 μM 33P-γ-ATP) is added and mixed with VX-509 stock solution. The reaction is initiated by the addition of an enzyme mixture [100 mM HEPES (pH 7.5), 10 mM MgCl2, 2 mM DTT, 0.02% BSA, 0.5 nM JAK3]. After 15 minutes, the reaction was quenched with 20% trichloroacetic acid (TCA). The quenched reaction was transferred to the GF/B filter plates and washed three times with 5% TCA. Following the addition of Ultimate Gold scintillant (50 μl), the samples were counted in a Packard TopCount gamma counter (PerkinElmer). In this procedure, the radioactivity trapped is a measure of the residual JAK3 kinase activity. From the activity versus concentration of VX-509 titration curve, the Ki value was determined by fitting the data to an equation for competitive tight binding inhibition kinetics using Prism software. |
| 體外活性 | ADH-1 (0.2 mg/mL) 阻斷胰腺癌細(xì)胞中 I 型膠原引發(fā)的變化，并且在阻止 N-cadherin 表達(dá)誘導(dǎo)的細(xì)胞運(yùn)動(dòng)方面表現(xiàn)出高效性。ADH-1 (0, 0.1, 0.2, 0.5 和 1.0 mg/mL) 以劑量依賴和 N-cadherin 依賴的方式誘導(dǎo)細(xì)胞凋亡[1]。 |
| 體內(nèi)活性 | ADH-1 (50 mg/kg) 顯著阻止了小鼠胰腺癌模型的腫瘤生長和轉(zhuǎn)移。在使用過表達(dá)N-cadherin的BxPC-3細(xì)胞的胰腺癌原位模型中，ADH-1防止了腫瘤細(xì)胞的侵襲和轉(zhuǎn)移[1]。在所評(píng)估的劑量下，ADH-1既沒有在大鼠主動(dòng)脈環(huán)實(shí)驗(yàn)中顯示出抗血管生成活性，也沒有在PC3皮下異種移植腫瘤模型中顯示出抗腫瘤潛力[2]。ADH-1 (10 mL/kg, i.p.) 增強(qiáng)了黑色素瘤腫瘤生長，但通過提高局部灌注的梅爾菲蘭的效果被克服。區(qū)域性灌注的替莫唑胺并不改變ADH-1對(duì)黑色素瘤腫瘤生長的增強(qiáng)作用。在A375（但非DM443）異種移植瘤中，ADH-1處理增加了絲氨酸473位點(diǎn)AKT的磷酸化，同時(shí)略微降低了兩種異種移植瘤中的N-cadherin表達(dá)[3]。 |
| 存儲(chǔ)條件 | Keep away from moisture,Keep away from direct sunlight,Store at low temperature,The compound is unstable in solution. Please use soon,
Powder: -20°C for 3 years
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 50 mg/mL (87.61 mM), Sonication is recommended.
10% DMSO+90% Saline : 5 mg/mL (8.76 mM), Solution.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (3.5 mM), Sonication is recommended.
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| 關(guān)鍵字 | N-cadherin | Inhibitor | inhibit | ADH-1 | ADH1 | ADH 1 |
| 相關(guān)產(chǎn)品 | Lycorine hydrochloride | ML327 | Aristolactam I | Raludotatug | PTA001_A4 | MC-1-F2 | Cadherin Peptide, avian Acetate | PF-03732010 | SD133 | BAS00093476 | RG-6125 | Tralokinumab |
| 相關(guān)庫 | 多肽分子庫 |