Structures of peptidomimetic ATG4B inhibitors

March 05, 2024

• Title:       

  Structures of peptidomimetic ATG4B inhibitors

• Image Source:

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

• Mark:

  Figure 1

• Associated context:

  Previously, we reported the identification of Z-FA-FMK (1, Figure 1) as a covalent active-site directed ATG4B inhibitor from a TR-FRET based focused library screening.The hit  expansion of 1 led to the discovery of Z-FG-FMK (2), which was 10-times more potent than 1 with an IC₅₀ of 1.2 μM in the biochemical assay.Herein we disclose the structure-guided optimization of 2 toward highly potent fluoromethylketone (FMK)-based ATG4B inhibitors.