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Mocetinostat(MGCD0103)在体外对广谱的人癌细胞系表现出有效的和选择性的抗增殖活性,并且这些作用需要HDAC抑制活性。在所有测试的细胞系中,Mocetinostat(MGCD0103)部分抑制细胞HDAC酶活性,尽管活性的最大抑制在细胞系中从总活性的75％至85％变化。 Mocetinostat在完整癌细胞中的IC50与组织来源无关。在A549细胞中,MGCD0103显示全细胞中HDAC活性的剂量依赖性抑制。在A549细胞中的高浓度下,Mocetinostat抑制最多80％的总活性。在HCT116细胞中,Mocetinostat诱导显着的S期耗竭以及G1和G2-M积累[1]。",{"key":227,"value":228},"体内研究","Mocetinostat(MGCD0103)以剂量依赖性方式显着抑制裸鼠中人肿瘤异种移植物的生长,并且抗肿瘤活性与肿瘤中组蛋白乙酰化的诱导相关。在每日施用13天后,Mocetinostat(MGCD0103)(2HBr盐)的po施用以剂量依赖性方式显着降低裸鼠中植入的晚期A549肿瘤的生长。 Mocetinostat(对于2HBr盐为170 mg\u002Fkg,相当于120 mg\u002Fkg游离碱)与单独载体治疗相比显着阻断了肿瘤的生长(在ANOVA Dunnett试验后P \u003C0.05),体重没有变化[1] 。",{"key":230,"value":231},"激酶实验","脱乙酰酶测定基于均相荧光释放测定。在室温下，将纯化的重组HDAC酶与在各种浓度下稀释的Mocetinostat（MGCD0103）在测定缓冲液[25mM HEPES（pH 8.0），137mM NaCl，1mM MgCl 2,2.7mM KCl]中孵育10分钟。将底物Boc-Lys（ε-Ac）-AMC（Bachem）加入到反应中，在37℃下进一步温育。对于HDAC酶的不同同种型，底物的浓度和孵育时间是不同的。在室温下孵育20分钟的胰蛋白酶允许从脱乙酰化的底物释放荧光团。通过荧光计在360nm的激发，470nm的发射和435nm的截止下检测荧光信号。通过分析剂量 - 反应抑制曲线[1]确定化合物的IC 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