Dey Anwesha, Tergaonkar Vinay, Lane David P
Laboratory of Cell Cycle Control, Institute of Molecular and Cell Biology, Proteos, 138673 Singapore.
Nat Rev Drug Discov. 2008 Dec;7(12):1031-40. doi: 10.1038/nrd2759.
The p53 and nuclear factor-kappaB (NF-kappaB) pathways play crucial roles in human cancer, in which inactivation of p53 and hyperactivation of NF-kappaB is a common occurrence. Activation of p53 and inhibition of NF-kappaB promotes apoptosis. Although drugs are being designed to selectively activate p53 or inhibit NF-kappaB, there is no concerted effort yet to deliberately make drugs that can simultaneously do both. Recent results suggest that a surprising selection of small molecules have this desirable dual activity. In this Review we describe the principles behind such dual activities, describe the current candidate molecules and suggest mechanisms and approaches to their further development.
p53和核因子-κB（NF-κB）通路在人类癌症中发挥着关键作用，其中p53失活和NF-κB过度激活屡见不鲜。激活p53并抑制NF-κB可促进细胞凋亡。尽管人们正在设计药物以选择性激活p53或抑制NF-κB，但尚未齐心协力专门研发出能同时实现这两种作用的药物。最近的研究结果表明，令人惊讶的是，有多种小分子具有这种理想的双重活性。在本综述中，我们描述了这种双重活性背后的原理，介绍了当前的候选分子，并提出了进一步开发它们的机制和方法。
