{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15(3)"],"submitter":["DeRatt LG"],"pubmed_abstract":["Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that affects many aspects essential to cell proliferation and survival. Recently, DHODH has been identified as a potential target for acute myeloid leukemia therapy. Herein, we describe the identification of potent DHODH inhibitors through a scaffold hopping approach emanating from a fragment screen followed by structure-based drug design to further improve the overall profile and reveal an unexpected novel binding mode. Additionally, these compounds had low P-gp efflux ratios, allowing for applications where exposure to the brain would be required."],"journal":["ACS medicinal chemistry letters"],"pagination":["381-387"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10945543"],"repository":["biostudies-literature"],"pubmed_title":["Discovery of Alternative Binding Poses through Fragment-Based Identification of DHODH Inhibitors."],"pmcid":["PMC10945543"],"pubmed_authors":["Pietsch EC","Jacoby E","Attar R","Edwards JP","Kazmi F","Kuduk SD","Matico R","Shaffer P","DeRatt LG","Tanner A","Wang W","Cisar JS"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of Alternative Binding Poses through Fragment-Based Identification of DHODH Inhibitors.","description":"Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that affects many aspects essential to cell proliferation and survival. Recently, DHODH has been identified as a potential target for acute myeloid leukemia therapy. Herein, we describe the identification of potent DHODH inhibitors through a scaffold hopping approach emanating from a fragment screen followed by structure-based drug design to further improve the overall profile and reveal an unexpected novel binding mode. Additionally, these compounds had low P-gp efflux ratios, allowing for applications where exposure to the brain would be required.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-02T18:06:34.785Z","creation":"2025-04-04T00:26:27.039Z"},"accession":"S-EPMC10945543","cross_references":{"pubmed":["38505861"],"doi":["10.1021/acsmedchemlett.3c00543"]}}