title: Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors.
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.
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Zongxing
authors: Z
authors: Qiu
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors: Bernd
authors: B
authors: Kuhn
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors: Johannes
authors: J
authors: Aebi
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Xianfeng
authors: X
authors: Lin
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Haiyuan
authors: H
authors: Ding
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Zheng
authors: Z
authors: Zhou
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Zhiheng
authors: Z
authors: Xu
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Danqing
authors: D
authors: Xu
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Li
authors: L
authors: Han
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Cheng
authors: C
authors: Liu
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Hongxia
authors: H
authors: Qiu
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Yuxia
authors: Y
authors: Zhang
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors: Wolfgang
authors: W
authors: Haap
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors: Claus
authors: C
authors: Riemer
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors: Martin
authors: M
authors: Stahl
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Ning
authors: N
authors: Qin
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Hong C
authors: HC
authors: Shen
authors: Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Shanghai , 720 Cailun Road, Shanghai 201203, China.
authors: Guozhi
authors: G
authors: Tang
keywords: ATG4B; autophagy; covalent inhibitor; fluoromethylketone; peptidomimetics