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mL,装载JNJ-7706621的胶束的IC50为6.3和1.6μg\u002F mL [3]。 JNJ-7706621显示对Aurora-A和Aurora-B的抑制,但在Plk1或Wee1丝氨酸\u002F苏氨酸激酶上测试的最高浓度下没有活性。 JNJ-7706621还显示出对所有人类癌细胞类型的体外有效生长抑制,IC50值范围为112至514nM [4]。",{"key":257,"value":258},"体内研究","JNJ-7706621(100mg\u002Fkg,ip)在A375(人黑素瘤)肿瘤异种移植模型中显示出95％的肿瘤生长抑制[1]。装载JNJ-7706621的胶束抑制肿瘤生长,并且比对照JNJ-7706621悬浮液更有效地延迟肿瘤生长[3]。 JNJ-7706621(100和125mg\u002Fkg)在间歇给药方案下在人肿瘤异种移植模型中是有效的[4]。",{"key":260,"value":261},"激酶实验","为了鉴定抑制CDK1激酶活性的化合物，使用CDK1 \u002F细胞周期蛋白B复合物开发筛选方法以磷酸化含有组蛋白H1的共有磷酸化位点的生物素化肽底物，其在体内被CDK1磷酸化。通过观察减少量的33P-g-ATP掺入链霉抗生物素蛋白包被的96孔闪烁微量培养板中的固定化底物来测量CDK1活性的抑制。将CDK1酶稀释于50mM Tris-HCl（pH 8），10mM MgCl 2,0.1mM Na 3 VO 4,1mM DTT，1％DMSO，0.25AM肽，每孔0.1 ACi 33P-g-ATP（2,000-3,000 Ci \u002F在存在或不存在各种浓度的测试化合物的情况下，在5mM ATP和5AM ATP下，在30℃下孵育1小时。通过用含有100mM EDTA的PBS洗涤终止反应，并在闪烁计数器中对板进行计数。使用测试化合物的抑制百分比的线性回归分析来确定IC 50值。极光激酶测定用10AM ATP和含有kemptide磷酸化基序的双重复的肽完成。",{"key":263,"value":264},"细胞实验","将HeLa细胞以每孔2500个活细胞的密度接种在96孔板中。然后将细胞与JNJ-7706621，装载JNJ-7706621的胶束和纳米颗粒的悬浮液一起孵育（JNJ-7706621浓度为0.011,0.022,0.11,0.22,1.1,2.2,11和22μg\u002F mL;稀释液在培养基）和无药物聚合物胶束（聚合物浓度0.3mg \u002F mL）和纳米颗粒（聚合物浓度5mg \u002F mL）4,24和48小时。使用MTT测试评估细胞毒性。使用酶标仪在570nm处测量吸光度。未处理的细胞作为对照，具有100％的活力，Triton X-100 1％用作细胞毒性的阳性对照。结果表示为五次测量的平均值±标准偏差。",{"key":266,"value":267},"动物实验","简而言之，在后肢中用1mm 3 A375肿瘤碎片皮下植入动物。在肿瘤达到62至126mg后，组成对匹配。从第1天开始给予动物JNJ-7706621或载体对照。遵循肿瘤生长延迟方法，其中当每只动物的肿瘤达到2.0g的预定大小时对每只动物实施安乐死。所有统计分析均使用非配对t检验进行，P水平为0.05（双尾）。",{"key":269,"value":270},"参考文献","[1].\nHuang S, et al. Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3639-41. Epub 2006 May 6.\n[2].\nMatsuhashi A, et al. Growth suppression and mitotic defect induced by JNJ-7706621, an inhibitor of cyclin-dependent kinases and aurora kinases. Curr Cancer Drug Targets. 2012 Jul;12(6):625-39.\n[3].\nDanhier F, et al. Active and passive tumor targeting of a novel poorly soluble cyclin dependent kinase inhibitor, JNJ-7706621. Int J Pharm. 2010 Jun 15;392(1-2):20-8.\n[4].\nEmanuel S, et al. The in vitro and in vivo effects of JNJ-7706621: a dual inhibitor of cyclin-dependent kinases and aurora kinases. 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