{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hunt JR"],"funding":["NCRR NIH HHS","National Cancer Institute","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["126788"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6942203"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(2)"],"pubmed_abstract":["Small molecule agonists of TLR7/8, such as imidazoquinolines, are validated agonists for the treatment of cancer and for use in vaccine adjuvants. Imidazoquinolines have been extensively modified to understand the structure-activity relationship (SAR) at the N1- and C2-positions resulting in the clinical drug imiquimod, resiquimod, and several other highly potent analogues. However, the SAR of the aryl ring has not been fully elucidated in the literature. This initial study examines the SAR of C7-substituted imidazoquinolines. These compounds not only demonstrated that TLR7/8 tolerate changes at the C7-position but can increase potency and change their cytokine profiles. The most notable TLR7/8 agonists developed from this study 5, 8, and 14 which are up to 4-fold and 2-fold more active th"],"journal":["Bioorganic & medicinal chemistry letters"],"pubmed_title":["Further exploration of the structure-activity relationship of imidazoquinolines; identification of potent C7-substituted imidazoquinolines."],"pmcid":["PMC6942203"],"funding_grant_id":["P50 GM069663","S10 RR014767","T32 GM008359","R01 CA173292"],"pubmed_authors":["Forrest ML","Prisinzano TE","Moulder KR","Hunt JR","Kleindl PA"],"additional_accession":[]},"is_claimable":false,"name":"Further exploration of the structure-activity relationship of imidazoquinolines; identification of potent C7-substituted imidazoquinolines.","description":"Small molecule agonists of TLR7/8, such as imidazoquinolines, are validated agonists for the treatment of cancer and for use in vaccine adjuvants. Imidazoquinolines have been extensively modified to understand the structure-activity relationship (SAR) at the N1- and C2-positions resulting in the clinical drug imiquimod, resiquimod, and several other highly potent analogues. However, the SAR of the aryl ring has not been fully elucidated in the literature. This initial study examines the SAR of C7-substituted imidazoquinolines. These compounds not only demonstrated that TLR7/8 tolerate changes at the C7-position but can increase potency and change their cytokine profiles. The most notable TLR7/8 agonists developed from this study 5, 8, and 14 which are up to 4-fold and 2-fold more active th","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jan","modification":"2026-05-03T00:50:29.857Z","creation":"2024-11-19T20:07:21.678Z"},"accession":"S-EPMC6942203","cross_references":{"pubmed":["31784317"],"doi":["10.1016/j.bmcl.2019.126788"]}}