New inhibitors of β-1,4-galactosyltransferase I discovered by virtual screening

Kranjc, Jaka (author), Tomašič, Tihomir (author), Pajk, Stane (author), Brinc, Matjaž (author), Pišlar, Anja (author), Anderluh, Marko (author)

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 IC$_{50}$ values were determined for the best performing inhibitors to obtain new chemotypes of β-1,4-GALT1 inhibitors.

• Language: English
• Keywords: β-1, 4-GALT1 inhibitors, galactosylation, β-1, 4-galactosyltransferase I, enzyme inhibitor, galactosyltransferase, UDP-Glo assay, virtual screening
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 6 str.
• Numbering: Vol. 20, iss. 7, art. e202400896
• PID: 20.500.12556/RUL-168197
• UDC: 615.4:54
• ISSN on article: 1860-7187
• DOI: 10.1002/cmdc.202400896
• COBISS.SI-ID: 223097859
• Publication date in RUL: 02.04.2025

Record is a part of a journal

• Title: ChemMedChem
• Shortened title: ChemMedChem
• Publisher: Wiley, Chemistry Europe
• ISSN: 1860-7187
• COBISS.SI-ID: 519053337

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: galaktoziltransferaza, galaktozilacija, zaviralci β-1, 4-GALT1, farmacevtska kemija