| 名稱 | Dacinostat |
| 描述 | LAQ824 (Dacinostat (NVP-LAQ824)) is a novel HDAC inhibitor with IC50 of 32 nM and is an activator of the p21 promoter. |
| 細(xì)胞實(shí)驗(yàn) | Cell proliferation is measured using an adaptation of published procedures (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfonyl)-2H-tetrazolium assay). The cells are seeded in 12-well dishes and cultured in RPMI 1640 containing 10% FBS. The cells are cultured in the presence of various concentrations of TSA (up to 1,000 ng/mL). To examine the growth inhibition by TSA, viable cell numbers are determined by trypan blue dye exclusion, counted in a Nesbauer-type hemocytometer for 0 hour, 24 hours, and 48 hours. The same amount of ethanol is added to the RPMI 1640 medium as the control experiment. All experiments are performed in duplicate and repeated 3 times The average background value (treatment with medium alone) is subtracted from each experimental well; triplicate values are averaged for each compound dilution. The following formulas are used to calculate the percentage of growth: If XT0, %Growth=(X-T0)/(GC-T0)*100. where T0 is the average value of T0 ? background, GC is the average value of untreated cells (in triplicate) ? background, and X is the average value of compound-treated cells (in triplicate)-background. The "% Growth" is plotted against compound concentration and used to calculate the IC50 using the linear regression techniques between data points to predict the concentration of compounds at 50% inhibition.(Only for Reference) |
| 激酶實(shí)驗(yàn) | In Vitro Histone Deacetylase Assay: HDAC enzymes are partially purified from H1299 cell lysate by ion exchange chromatography using the Q Sepharose Fast Flow column. Enzyme complexes are collected from 500 mg of total cell lysate by immunoprecipitation with cdk2 polyclonal antibody or cdk1/cdc2 monoclonal antibody. Immunoprecipitates are resuspended in kinase buffer (50 mM Hepes, pH 8, 10 mM MgCl2, 2.5 mM EDTA, 1 mM dithiothreitol, 20 mM ATP, 10 mM β-glycerophosphate, 0.1 mM NaVO4, 1 mM sodium fluoride, 50 mM ATP, 10 μCi of [γ-32P]ATP) along with 1 μg of pRb recombinant protein substrate (cdk2) or 10 mL of H1 histone mixture containing 20 μg of substrate (cdc2). Phosphorylated Rb and H1 histone are resolved by electrophoresis and quantitated using a PhosphorImager. |
| 體外活性 | 100 mg/kg LAQ824劑量依賴性抑制攜帶HCT116和人結(jié)腸癌移植瘤的裸鼠腫瘤生長,且無細(xì)胞毒性. |
| 體內(nèi)活性 | LAQ824誘導(dǎo)A549細(xì)胞中p21蛋白的劑量依賴性增加和Rb腫瘤抑制因子的低磷酸化狀態(tài)的增加。LAQ824在IL-10基因啟動(dòng)子水平誘導(dǎo)染色質(zhì)改變,導(dǎo)致增強(qiáng)的轉(zhuǎn)錄抑制因子HDAC11和PU.1的募集并抑制BALB/c鼠巨噬細(xì)胞中IL-10的產(chǎn)生。此外,LAQ824通過激活p21啟動(dòng)子,也激活編碼p21細(xì)胞周期抑制劑的基因表達(dá),最大啟動(dòng)子活性AC50為50%時(shí),濃度為0.30 μM。 LAQ824抑制H1299（一種非小細(xì)胞肺癌細(xì)胞系）和HCT116（一種結(jié)腸癌細(xì)胞系）的細(xì)胞生長,IC50分別為0.15 μM和0.01 μM,LAQ824的抗增殖作用對(duì)腫瘤細(xì)胞系具有選擇性,同時(shí)僅在正常成纖維細(xì)胞中誘導(dǎo)生長停滯。 |
| 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 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 40 mg/mL (105.42 mM), Sonication is recommended.
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| 關(guān)鍵字 | LAQ 824 | LAQ-824 | NVP-LAQ 824 | NVP-LAQ-824 | Histone deacetylases | inhibit | Autophagy | HDAC | Inhibitor | Dacinostat |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Taurine | Gefitinib | Hydroxychloroquine | Curcumin | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
| 相關(guān)庫 | 抑制劑庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | ReFRAME 相關(guān)化合物庫 | 抗衰老化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 人代謝物化合物庫 | 抗癌藥物庫 |