Substrate interaction inhibits γ-secretase production of amyloid-β peptides

Jing Zhao, Yuanyuan Xiao, Xinyue Liu, Soohyun Kim, Xianzhong Wu, Marilia Barros, Ran Zhuang, Xuben Hou, Yingkai Zhang, Nikolaos K. Robakis, Yue Ming Li, Jonathan S. Dordick, Iban Ubarretxena-Belandia, Chunyu Wang

Research output: Contribution to journalArticlepeer-review


Combining NMR, mass spectrometry, AlphaLISA and cell assays, we discovered a compound C1 that binds C-terminal juxtamembrane lysines at the transmembrane domain of the amyloid precursor protein (APPTM) and inhibits γ-secretase production of amyloid-β with μM IC50. Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery.

Original languageEnglish (US)
Pages (from-to)2578-2581
Number of pages4
JournalChemical Communications
Issue number17
StatePublished - Feb 28 2020

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • General Chemistry
  • Ceramics and Composites
  • Metals and Alloys
  • Materials Chemistry
  • Surfaces, Coatings and Films
  • Catalysis


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