2. Academic Validation
  3. Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors

Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors

  • ACS Med Chem Lett. 2016 Jun 25;7(8):802-6. doi: 10.1021/acsmedchemlett.6b00208.
Zongxing Qiu 1,  Bernd Kuhn 2,  Johannes Aebi 2,  Xianfeng Lin 1,  Haiyuan Ding 1,  Zheng Zhou 1,  Zhiheng Xu 1,  Danqing Xu 1,  Li Han 1,  Cheng Liu 1,  Hongxia Qiu 1,  Yuxia Zhang 1,  Wolfgang Haap 2,  Claus Riemer 2,  Martin Stahl 2,  Ning Qin 1,  Hong C Shen 1,  Guozhi Tang 1
Affiliations

Affiliations

  • 1 Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
  • 2 Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, 4070 Basel, Switzerland.
PMID: 27563406 DOI: 10.1021/acsmedchemlett.6b00208
Abstract

ATG4B or autophagin-1 is a cysteine protease that cleaves ATG8 family proteins. ATG4B plays essential roles in the autophagosome formation and the Autophagy pathway. Herein we disclose the design and structural modifications of a series of fluoromethylketone (FMK)-based peptidomimetics as highly potent ATG4B inhibitors. Their structure-activity relationship (SAR) and protease selectivity are also discussed.

Keywords

ATG4B; autophagy; covalent inhibitor; fluoromethylketone; peptidomimetics.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100522
    ≥98.0%, Autophagin-1 Inhibitor