Expert Opin Ther Pat. 2011 Mar;21(3):287-94. doi: 10.1517/13543776.2011.546349.
Most researchers have sought to restore the activity of p53 by identifying small molecules able to block the interaction of p53 with mouse double minute 2 (MDM2). To the same end, some scientists are pursuing the development of compounds that can inhibit the ubiquitin-ligase (E3) activity of MDM2. In this article, we provide a perspective review on what is known about MDM2 E3 inhibitors and what major questions remain to be addressed to boost this line of research. Recent studies provide the proof of concept that the inhibition of MDM2 E3 activity represents a viable strategy for rescuing p53 activity from MDM2 inhibitory functions. It is likely that settling some open issues such as the site of action of these compounds and their specificity towards E3 ligase enzymes will open in the near feature new horizons in cancer therapy.
大多数研究人员试图通过鉴定能够阻断 p53 与鼠双微体 2（MDM2）相互作用的小分子来恢复 p53 的活性。为此，一些科学家正在致力于开发能够抑制 MDM2 泛素连接酶（E3）活性的化合物。在本文中，我们对 MDM2 E3 抑制剂的已知情况以及为推动这一研究领域还需要解决的主要问题提供了一个观点综述。最近的研究提供了概念验证，即抑制 MDM2 E3 活性代表了从 MDM2 抑制功能中恢复 p53 活性的一种可行策略。很可能解决这些化合物的作用部位及其对 E3 连接酶的特异性等一些悬而未决的问题，将在不久的将来为癌症治疗开辟新的前景。
