20.500.12556/RUL-137516 Discovery of a new drug-like series of OGT inhibitors by virtual screening O-GlcNAcylation is an essential post-translational modification installed by the enzyme O-β-N-acetyl-d-glucosaminyl transferase (OGT). Modulating this enzyme would be extremely valuable to better understand its role in the development of serious human pathologies, such as diabetes and cancer. However, the limited availability of potent and selective inhibitors hinders the validation of this potential therapeutic target. To explore new chemotypes that target the active site of OGT, we performed virtual screening of a large library of commercially available compounds with drug-like properties. We purchased samples of the most promising virtual hits and used enzyme assays to identify authentic leads. Structure-activity relationships of the best identified OGT inhibitor were explored by generating a small library of derivatives. Our best hit displays a novel uridine mimetic scaffold and inhibited the recombinant enzyme with an IC50 value of 7 µM. The current hit represents an excellent starting point for designing and developing a new set of OGT inhibitors that may prove useful for exploring the biology of OGT. O-GlcNAc transferase OGT inhibitors virtual screening pharmaceutical chemistry O-GlcNAc transferaza zaviralci OGT virtualno rešetanje farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2022-06-20 11:31:48 2022-06-20 11:31:52 2025-08-08 13:20:42 0000-00-00 00:00:00 2022 0 0 21 str. iss. 6, art 1996 Vol. 27 2022 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54 1420-3049 10.3390/molecules27061996 101699843 molecules-27-01996-v3.pdf molecules-27-01996-v3.pdf 1 39D01ECF24B3BB2C66A98BE71134677D 6fd6f65e67008269d29425cd3e008194316fe82e3d391fd61b7e47e0f7cedabd f0c29856-f07b-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=157486 https://www.mdpi.com/1420-3049/27/6/1996 1 c144ba29-3031-11ed-92af-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=160680 Fakulteta za farmacijo 0 0 0