这些联合用药的尝试与研究也确实达到了较好的效果。HDAC可改变染色质形态进而调节基因转录。若该酶活性失调,则细胞原有的基因表达平衡状态就会被打破,从而导致一些列调控细胞周期和细胞增殖的因子表达失衡,进而导致细胞恶变。HDACs抑制剂(HDACi)可有效抑制肿瘤细胞的增长,诱导末端分化以及癌细胞的凋亡,成为肿瘤治疗领域的BVD-523订单重要手段。Vorinostat (SAHA)于2006年被美国FDA批准治疗皮肤T-细胞淋巴瘤。然而,I/II期临床结果显示,由于SAHA的选择性低引起许多副作用而且对于某些实体瘤响应较低。研究证实,CDKs抑制剂可有效降低HDACs抑制剂引起的副作用。CDKs是一类依赖细胞周期蛋白(cycl{Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|selleck Anti-infection Compound Library|selleck Antiinfection Compound Library|selleck Anti-infection Compound Library|selleck Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|buy Anti-infection Compound Library|Anti-infection Compound Library半抑制浓度|Anti-infection Compound Library价格|Anti-infection Compound Library花费|Anti-infection Compound Library溶解度|Anti-infection Compound Library购买|Anti-infection Compound Library制造商|Anti-infection Compound Library查找购买|Anti-infection Compound Library订单|Anti-infection Compound Library mouse|Anti-infection Compound Library chemical structure|Anti-infection Compound Library分子量|Anti-infection Compound Library molecular weight|Anti-infection Compound Library数据表|Anti-infection Compound Library supplier|Anti-infection Compound Library体外|Anti-infection Compound Library细胞系|Anti-infection Compound Library concentration|Anti-infection Compound Library nmr|Anti-infection Compound Library体内|Anti-infection Compound Library clinical trial|Anti-infection Compound Library cell assay|Anti-infection Compound Library screening|Anti-infection Compound Library high throughput|buy Antiinfection Compound Library|Antiinfection Compound Library半抑制浓度|Antiinfection Compound Library价格|Antiinfection Compound Library花费|Antiinfection Compound Library溶解度|Antiinfection Compound Library购买|Antiinfection Compound Library制造商|Antiinfection Compound Library查找购买|Antiinfection Compound Library订单|Antiinfection Compound Library chemical structure|Antiinfection Compound Library数据表|Antiinfection Compound Library supplier|Antiinfection Compound Library体外|Antiinfection Compound Library细胞系|Antiinfection Compound Library concentration|Antiinfection Compound Library clinical trial|Antiinfection Compound Library cell assay|Antiinfection Compound Library screening|Antiinfection Compound Library high throughput|Anti-infection Compound high throughput screening|in)的丝／苏氨酸蛋白激酶,其功能改变导致的细胞周期紊乱在癌症发病机制中经常被观察到。目前为止,CDK家族已有超过20个成员被发现。CDKs不仅在细胞周期调节过程中发挥至关重要的作用,而且是细胞转录过程中的重要调节因子。本文结合SAHA和化合物30(CDK抑制剂)的功能团特征,设计和合成了一些不列嘧啶苄基异羟肟酸类双靶点抑制剂。首先,以芳基乙酮为原料,经多步亲核加成-消除,亲核取代,氧化等反应得到关键中间体羧酸甲酯,该中间体在羟胺钾甲醇溶液中反应得到目标化合物。本论文中共合成新化合物55个,其中目标化合物28个,新中间体27个。初期体外酶活性测定结果显示,多数化合物具有与SAHA相当甚至优于SAHA的HDACs抑制活性,部分化合物表现出一定的CDK9抑制活性。