Sausville Edward A
University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene St. Baltimore, MD 21201, USA.
Curr Top Med Chem. 2005;5(12):1109-17. doi: 10.2174/156802605774370874.
Since a prior review of cell cycle inhibitors developed at the National Cancer Institute, continued progress in the application of these molecules has been pursued. Evidence of preliminary activity on the part of flavopiridol in certain chronic leukemias has pointed to that disease area as of potential interest, but likely by affecting transcriptional regulation through non-cell cycle-related CDKs. Brief duration infusion early phase trials with UCN-01, and combination studies with cytotoxics are commencing. Emerging structural data has refined the basis for screening strategies directed at cell cycle regulatory kinases, including cdks, chk kinases and most recently the mitotic phase aurora kinases. This interval progress report will review and update progress in these related but distinct drug discovery and development interest areas.
自美国国立癌症研究所对细胞周期抑制剂进行了先前的综述以来，一直在追求这些分子应用方面的持续进展。黄酮哌啶醇在某些慢性白血病中初步活性的证据表明该疾病领域具有潜在兴趣，但可能是通过非细胞周期相关的细胞周期蛋白依赖性激酶（CDK）影响转录调控。UCN - 01的短时间输注早期试验以及与细胞毒性药物的联合研究正在开展。新出现的结构数据完善了针对细胞周期调节激酶（包括CDK、Chk激酶以及最近的有丝分裂期极光激酶）的筛选策略基础。这份阶段性进展报告将回顾并更新这些相关但不同的药物发现和开发兴趣领域的进展。
