名称 | Tubastatin A |
描述 | Tubastatin A (Tubastatin A BASE) is an effective and specific HDAC6 inhibitor (IC50: 15 nM, in a cell-free assay). Its selectivity is 1000-fold against all the other isozymes except HDAC8. |
细胞实验 | Anchorage-independent growth is assessed by growing cells in soft agar. About 25,000 cells suspended in 0.4% agar in culture media are layered over a 1% agar layer in a 6-well plate. Media are added twice a week and pictures are taken after 21 days of incubation. The number and size of colonies are analyzed using the Gel-Pro software.(Only for Reference) |
激酶实验 | HDAC enzymatic assays: Tubastatin A is dissolved and diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, and 20 μM tris(2-carboxyethyl)phosphine) to 6-fold of the final concentration. HDAC enzymes are diluted to 1.5-fold of the final concentration in assay buffer and pre-incubated with Tubastatin A for 10 minutes before the addition of the substrate. The amount of FTS (HDAC1, HDAC2, HDAC3, and HDAC6) or MAZ-1675 (HDAC4, HDAC5, HDAC7, HDAC8, and HDAC9) used for each enzyme is equal to the Michaelis constant (Km), as determined by a titration curve. FTS or MAZ-1675 is diluted in assay buffer to 6-fold the final concentration with 0.3 μM sequencing grade trypsin. The substrate/trypsin mix is added to the enzyme/compound mix and the plate is shaken for 60 seconds and then placed into a SpectraMax M5 microtiter plate reader. The enzymatic reaction is monitored for release of 7-amino-4-methoxy-coumarin over 30 minutes, after deacetylation of the lysine side chain in the peptide substrate, and the linear rate of the reaction is calculated. |
体外活性 | 与对照组相比,Tubastatin A 可使PCNA阳性细胞的量显著降低(34% vs 65%).在同基因大鼠原位胆管癌模型中,Tubastatin A(10 mg/kg)降低瘤重与肝重和体重(分别为5和5.6倍)的比值.在给弗氏完全佐剂诱导的动物炎症模型中,Tubastat A(30 mg/kg,i.p.)对鼠爪体积有显著抑制作用.Tubastat A(30 mg/kg,i.p.)处理胶原诱导型关节炎DBA1小鼠的爪子组织,使临床评分(70%)和IL-6表达显著降低. |
体内活性 | Tubastatin A(5 μM)剂量依赖性地使神经元细胞免于同型半胱氨酸诱导的死亡,10 μM时可完全避免。 Tubastatin A(10 μM)对组蛋白乙酰化有轻微诱导作用。作用于胆管癌细胞系时,Tubastatin A(10 μM)促使乙酰化α-tubulin水平增加和初级纤毛表达的恢复,初级纤毛表达的恢复与Hedgehog、MAPK信号通路下调、细胞增殖率(平均50%)和浸润(40%)减少相关。作用于脂多糖刺激的人类 THP-1巨噬细胞时,Tubastatin A明显抑制TNF-α和IL-6(IC50:272/712 nM)。作用于小鼠Raw 264.7巨噬细胞时,Tubastatin A剂量依赖性抑制一氧化氮分泌(IC50:4.2 μM)。 |
存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
溶解度 | DMSO : 35 mg/mL (104.35 mM), Sonication is recommended. Ethanol : < 1 mg/mL (insoluble or slightly soluble) H2O : < 1 mg/mL (insoluble or slightly soluble)
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关键字 | Autophagy | Inhibitor | Apoptosis | inhibit | HDAC | Histone deacetylases | Tubastatin A |
相关产品 | Guanidine hydrochloride | Naringin | Valproic Acid | L-Glutamic acid | Gefitinib | Hydroxychloroquine | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | L-Ascorbic acid | Paeonol | Sodium 4-phenylbutyrate |
相关库 | 抑制剂库 | 经典已知活性库 | 已知活性化合物库 | 自噬库 | 细胞凋亡化合物库 | 抗衰老化合物库 | 高选择性抑制剂库 | HIF-1化合物库 | NF-κB 通路分子库 | 细胞重编程化合物库 |