{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Modi G"],"funding":["National Institute of Allergy and Infectious Diseases","U.S. Department of Energy","NIAID NIH HHS","Brandeis University"],"pagination":["3062-3076"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9575405"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(11)"],"pubmed_abstract":["Many bacterial pathogens, including <i>Staphylococcus aureus</i>, require inosine 5'-monophosphate dehydrogenase (IMPDH) for infection, making this enzyme a promising new target for antibiotics. Although potent selective inhibitors of bacterial IMPDHs have been reported, relatively few have displayed antibacterial activity. Here we use structure-informed design to obtain inhibitors of <i>S. aureus</i> IMPDH (<i>Sa</i>IMPDH) that have potent antibacterial activity (minimal inhibitory concentrations less than 2 μM) and low cytotoxicity in mammalian cells. The physicochemical properties of the most active compounds were within typical Lipinski/Veber space, suggesting that polarity is not a general requirement for achieving antibacterial activity. Five compounds failed to display activity in m"],"journal":["ACS infectious diseases"],"pubmed_title":["The Enzymatic Activity of Inosine 5'-Monophosphate Dehydrogenase May Not Be a Vulnerable Target for <i>Staphylococcus aureus</i> Infections."],"pmcid":["PMC9575405"],"funding_grant_id":["DE-AC02-06CH11357","1R21AI138048","Sprout Award","R21 AI138048","HHSN272201700060C","R01 AI125362","R01AI125362"],"pubmed_authors":["Hedstrom L","Joachimiak A","Rothstein DM","Cullinane RT","Zhang M","Lawson AP","Cuny GD","Marqus GM","Manna AC","Zhang Y","Kuzmic P","Kim Y","Snider BB","Wang X","Cheung A","Vippila MR","Chacko S","Maltseva N","Kotler JLM","Modi G","Gollapalli DR"],"additional_accession":[]},"is_claimable":false,"name":"The Enzymatic Activity of Inosine 5'-Monophosphate Dehydrogenase May Not Be a Vulnerable Target for <i>Staphylococcus aureus</i> Infections.","description":"Many bacterial pathogens, including <i>Staphylococcus aureus</i>, require inosine 5'-monophosphate dehydrogenase (IMPDH) for infection, making this enzyme a promising new target for antibiotics. Although potent selective inhibitors of bacterial IMPDHs have been reported, relatively few have displayed antibacterial activity. Here we use structure-informed design to obtain inhibitors of <i>S. aureus</i> IMPDH (<i>Sa</i>IMPDH) that have potent antibacterial activity (minimal inhibitory concentrations less than 2 μM) and low cytotoxicity in mammalian cells. The physicochemical properties of the most active compounds were within typical Lipinski/Veber space, suggesting that polarity is not a general requirement for achieving antibacterial activity. Five compounds failed to display activity in m","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2026-05-27T19:09:13.265Z","creation":"2025-02-19T03:22:53.024Z"},"accession":"S-EPMC9575405","cross_references":{"pubmed":["34590817"],"doi":["10.1021/acsinfecdis.1c00342"]}}