1. Academic Validation
  2. 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.
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抑制剂