3 years ago

Discovery of a novel class of pyridine derivatives that selectively inhibits mutant Isocitrate dehydrogenase 2

Discovery of a novel class of pyridine derivatives that selectively inhibits mutant Isocitrate dehydrogenase 2
Zhuolin Li, Guoyi Yan, Tao Zhang, Mingxing Hu, Yuanwei Chen, Fangying Wang, Lifeng Zhao, Yinglan Zhao
Current paper presents synthesis and Structure-Activity Relationship of pyridine derivatives as inhibitors of mutant isocitrate dehydrogenase 2 (IDH2). A series of 2,4,6-trisubsitituted pyridine derivatives have been prepared and evaluated in vitro. Among these compounds, 14n exhibited excellent inhibition activity with the IC50 of 54.6 nM, which is approximately 1-fold improvement compared to drug candidate AG-221 (Enasidenib) that is in Phase III trial. Exquisite selectivity of 14n for IDH2 R140Q mutant isoform was demonstrated by the poor activity against the wild-type IDH1 and IDH2. This article is protected by copyright. All rights reserved. Thirty-six 2,4,6-trisubsitituted pyridine derivatives have been prepared and evaluated in vitro. Among these compounds, 14n exhibited excellent inhibition activity with the IC50 of 54.6 nM, which is approximately 1-fold improvement compared to drug candidate AG-221 (Enasidenib) that is in Phase III trial.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.13139

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.