College of Pharmacy, Medicinal Chemistry and Molecular Pharmacology, 575 W Stadium Ave, Purdue University, West Lafayette, IN 47907, USA.
Center for Cancer Research, Purdue University, 201 S University St, West Lafayette, IN 47906, USA.
Molecules. 2021 Jul 7;26(14):4132. doi: 10.3390/molecules26144132.
This review is dedicated to Professor William A. Denny's discovery of XR5944 (also known as MLN944). XR5944 is a DNA-targeted agent with exceptionally potent antitumor activity and a novel DNA binding mode, bis-intercalation and major groove binding, as well as a novel mechanism of action, transcription inhibition. This novel anticancer compound represents a remarkable accomplishment resulting from two decades of drug discovery by Professor Denny and coworkers. Here, we review our work on the structural study of the DNA binding mode of XR5944 and mechanistic study of XR5944 action.
这篇综述是献给 William A. Denny 教授发现 XR5944（也称为 MLN944）的。XR5944 是一种 DNA 靶向剂，具有极强的抗肿瘤活性和新颖的 DNA 结合模式，即双嵌入和大沟结合，以及新颖的作用机制，转录抑制。这种新型抗癌化合物是 Denny 教授及其同事进行了二十年的药物发现的杰出成果。在这里，我们回顾了我们在 XR5944 的 DNA 结合模式的结构研究和 XR5944 作用的机制研究方面的工作。
