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Updated: Sep 17, 2025

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
Published on: November 11, 2016
α-Heteroarylthiomethyl ketones: Small molecule inhibitors of 3CLpro
Damijan Knez1, Matic Proj1, Krištof Bozovičar2
11University of Ljubljana, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, 1000 Ljubljana, Slovenia.
Abstract:
The main protease 3CLpro of the SARS-CoV-2 virus is a well--established therapeutic target for the treatment of COVID-19. In this study, we screened an in-house compound library and identified a series of α-heteroarylthiomethyl ketones as inhibitors of 3CLpro. Among these, analogues 31 and 33 emerged as the most interesting candidates with IC 50 values of 95.4 ± 3.1 and 95.0 ± 6.9 µmol L- 1, respectively. Preliminary in vitro studies suggest a potential covalent mode of inhibition, although further studies are required to confirm this mechanism. These findings provide a new chemical scaffold for the development of 3CLpro-targeting inhibitors.
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