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

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

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.

• Jezik: Angleški jezik
• Ključne besede: β-1, 4-GALT1 inhibitors, galactosylation, β-1, 4-galactosyltransferase I, enzyme inhibitor, galactosyltransferase, UDP-Glo assay, virtual screening
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: 6 str.
• Številčenje: Vol. 20, iss. 7, art. e202400896
• PID: 20.500.12556/RUL-168197
• UDK: 615.4:54
• ISSN pri članku: 1860-7187
• DOI: 10.1002/cmdc.202400896
• COBISS.SI-ID: 223097859
• Datum objave v RUL: 02.04.2025

Gradivo je del revije

• Naslov: ChemMedChem
• Skrajšan naslov: ChemMedChem
• Založnik: Wiley, Chemistry Europe
• ISSN: 1860-7187
• COBISS.SI-ID: 519053337

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: galaktoziltransferaza, galaktozilacija, zaviralci β-1, 4-GALT1, farmacevtska kemija