{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Anwar MM"],"funding":["MICIU/AEI/10.13039/501100011033 and by ERDF/EU","EMERGIA 2021 program from the Andalusian Regional Government-Junta de Andalucía","MICIU/AEI/10.13039/501100011033","MCIN/AEI/10.13039/501100011033","CIDEGENT Excellent Research Program of the Valencian regional government","Instituto de Salud Carlos III cofunded with ERDF","Fundació la Marató de TV3"],"pagination":["292"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12534982"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(1)"],"pubmed_abstract":["Human dihydroorotate dehydrogenase (DHODH) is the rate-limiting enzyme in pyrimidine de novo synthesis and represents a promising target for cancer therapy. However, current inhibitors of DHODH have limited clinical effectiveness and adverse effects. Herein, we report NK-A 17E-233I, a novel small-molecule inhibitor of the human DHODH enzyme, identified through a prospective virtual screening methodology. Molecular docking and biochemical assays show NK-A 17E-233I functions as a pure or partial competitive inhibitor with respect to the natural substrate, dihydroorotate (DHO). It adopts a distinct binding mode from classical inhibitors that target the flavin mononucleotide (FMN) binding cavity of the hydrophobic tunnel. NK-A 17E-233I exhibits selective cytotoxicity in both human cancer cell "],"journal":["Journal of experimental & clinical cancer research : CR"],"pubmed_title":["NK-A 17E-233I: a novel competitive inhibitor of human dihydroorotate dehydrogenase (DHODH) for cancer therapy."],"pmcid":["PMC12534982"],"funding_grant_id":["PID2022-140899NB-I00","PID2022-136791NB-I00","CNS2024-154649","CIDEGENT/2021/026","EMC21_00057","PI21/00554","202020-30-31"],"pubmed_authors":["Garcia-Rodriguez N","Verma S","Sagadevan S","Angione C","Occhipinti A","Marti R","Knecht W","Ordonez-Moran P","Juanes MA","Sele C","Huertas P","Meseguer S","Krupinska E","Anwar MM","Ramon J","Rodriguez-Jimenez A"],"additional_accession":[]},"is_claimable":false,"name":"NK-A 17E-233I: a novel competitive inhibitor of human dihydroorotate dehydrogenase (DHODH) for cancer therapy.","description":"Human dihydroorotate dehydrogenase (DHODH) is the rate-limiting enzyme in pyrimidine de novo synthesis and represents a promising target for cancer therapy. However, current inhibitors of DHODH have limited clinical effectiveness and adverse effects. Herein, we report NK-A 17E-233I, a novel small-molecule inhibitor of the human DHODH enzyme, identified through a prospective virtual screening methodology. Molecular docking and biochemical assays show NK-A 17E-233I functions as a pure or partial competitive inhibitor with respect to the natural substrate, dihydroorotate (DHO). It adopts a distinct binding mode from classical inhibitors that target the flavin mononucleotide (FMN) binding cavity of the hydrophobic tunnel. NK-A 17E-233I exhibits selective cytotoxicity in both human cancer cell ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-05-09T03:21:35.079Z","creation":"2026-05-09T03:11:54.469Z"},"accession":"S-EPMC12534982","cross_references":{"pubmed":["41107985"],"doi":["10.1186/s13046-025-03538-w"]}}