| 名稱 | CVT-313 |
| 描述 | CVT-313 (NG-26) is a potent, selective, reversible, and ATP-competitive inhibitor. |
| 細(xì)胞實(shí)驗(yàn) | CVT313 is prepared in DMSO and stored, and then diluted with appropriate medium before use[2]. MRC-5 cells are grown in Dulbecco's modified Eagle's medium containing 5% fetal calf serum. CVT313 (0, 5, 10, 15 μM) is added to exponentially growing cells in tissue culture. Cell population is measured. Proliferation assays are carried out using the nonradioactive CellTiter 96 kit after 48-h exposure. For FACS analysis of DNA content, cells are trypsinized, fixed in 70% ice-cold ethanol, and treated with 0.1 mg/mL RNase A and 40 μg/mL propidium iodide for 1 h at 37°C[2]. |
| 激酶實(shí)驗(yàn) | For kinase assays, purified CDC5L(295-795)-His6 is mixed with [γ-32P]ATP, COS-7 cell extract, and incubated in 100 μL 20 mM HEPES, pH 7.5, 50 mM NaCl, 2 mM MnCl2, 10 mM MgCl2, 0.5% NP-40, 0.5 mM PMSF, 5 mM benzamidine hydrochloride, 5 mM NaF, 1 mM NaVO3 and the specific inhibitor at 30°C for 10 minutes. Cell extract as a source of kinase activity is prepared from subconfluent, serum-stimulated COS-7 cells lysed in 20 mM HEPES-NaOH, pH 7.5, 50 mM NaCl, 1% Triton X-100, 10% glycerol, protease and phosphotase inhibitors. Phosphorylated proteins are separated by electrophoresis in 15% polyacrylamide-SDS gels. Specific inhibitors included 20 μM staurosporine, 10 μM genistein, 1 μM CVT-313, 10 μM Rp-MB-cAMPS and 50 μM PD98059[1]. |
| 體外活性 | CVT-313已顯示在抑制其他激酶方面的作用，但其IC50值相較于CDK2 (IC50=0.5 μM)顯著較高，具體包括CDK1 (IC50=4.2 μM)、CDK4 D1 (IC50=215 μM)以及MAPK/PKA/PKC (IC50>1.25 mM)。研究表明，CVT-313在5-20 μM濃度下對(duì)細(xì)胞增殖有顯著影響[1]。CVT-313是從嘌呤類似物庫中篩選出的一種強(qiáng)效CDK2抑制劑，體外IC50為0.5 μM。其抑制作用與ATP競爭性相關(guān)(Ki=95 nM)，且表現(xiàn)出對(duì)于非相關(guān)ATP依賴性絲氨酸/蘇氨酸激酶無影響的選擇性。當(dāng)添加至CDK1或CDK4時(shí)，需CVT-313濃度分別增至8.5倍和430倍才能實(shí)現(xiàn)酶活性的半最大抑制。通過使用正常及腫瘤人類/鼠類細(xì)胞系，對(duì)CVT-313對(duì)細(xì)胞增殖的影響進(jìn)行了測量，其生長抑制的IC50范圍為1.25至20 μM[2]。 |
| 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 (124.85 mM)
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| 關(guān)鍵字 | inhibit | CDK | Cyclin dependent kinase | NG-26 | CVT-313 | NG 26 | Inhibitor |
| 相關(guān)產(chǎn)品 | Sodium Oxamate | Ribociclib | Palbociclib monohydrochloride | Abemaciclib methanesulfonate | CASIN | Olomoucine | Palbociclib | GW 441756 | Dinaciclib | Ro-3306 | GSK 3 Inhibitor IX | Abemaciclib |
| 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 | 抗心血管疾病化合物庫 | 抗衰老化合物庫 | NO PAINS 化合物庫 | 臨床前化合物庫 |