Kranjc, Jaka, Tomašič, Tihomir, Pajk, Stane, Brinc, Matjaz, Pišlar, Anja and Anderluh, Marko (2025) New Inhibitors of β-1,4-Galactosyltransferase I Discovered by Virtual Screening. ChemMedChem, 20 (7). e202400896. ISSN 1860-7187

Abstract

Seven different enzymes comprise the galactosyltransferases family, of which β-1,4-galactosyltransferase I (β-1,4-GALT1) is the major contributor to galactosylation activity in cells. Since abnormalities in galactosylation are associated with many pathophysiological conditions, β-1,4-GALT1 is an interesting new target for drug discovery and molecular probe design. There are several known β-1,4-GALT1 inhibitors, but most of them suffer from low cell permeability and thus low in vivo activity. In the present work, we describe an in silico screening performed using commercially available virtual compound libraries that led us to the discovery of novel β-1,4-GALT1 inhibitors. A virtual screening campaign was performed by docking compound libraries to the binding site of β-1,4-GALT1, followed by biological evaluation of selected hits for their β-1,4-GALT1 inhibitory activity. The IC50 values were determined for the best performing inhibitors to obtain new chemotypes of β-1,4-GALT1 inhibitors.

Item Type:	Article
Keywords:	Galactosyltransferases Enzyme Inhibitors Humans Structure-Activity Relationship Molecular Docking Simulation Drug Evaluation, Preclinical Molecular Structure Small Molecule Libraries Binding Sites Drug Discovery Dose-Response Relationship, Drug
Date Deposited:	18 Apr 2025 00:45
Last Modified:	18 Apr 2025 00:45
URI:	https://oak.novartis.com/id/eprint/55665