{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kalebic D"],"funding":["NIAID NIH HHS","Defense Threat Reduction Agency/Fundamental Research to Counter Weapons of Mass Destruction, and the Department of Defense/Congressionally Directed Medical Research Programs"],"pagination":["1341"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12472322"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(9)"],"pubmed_abstract":["<b>Background/Objectives</b>: RMC-113, a 3-alkynyl-6-aryl-disubstituted isothiazolo[4,3-<i>b</i>]pyridine, is a dual inhibitor of the lipid kinases PIKfyve and PIP4K2C with broad-spectrum antiviral activity. The aim was to study the structure-activity relationship (SAR) of isothiazolo[4,3-<i>b</i>]pyridines as dual PIKfyve/PIP4K2C inhibitors. <b>Methods</b>: A series of isothiazolo[4,3-<i>b</i>]pyridines was synthesized by introducing structural variety at positions 3 and 6 of the central scaffold. The primary assay to guide the synthetic chemistry was a biochemical PIKfyve assay, with a number of analogues also tested for PIP4K2C binding affinity. Finally, isothiazolo[4,3-<i>b</i>]pyridines were also evaluated for antiviral and antitumoral activity in cell-based assays. <b>Results</b>: PI"],"journal":["Pharmaceuticals (Basel, Switzerland)"],"pubmed_title":["Structure-Activity Relationship Study of 3-Alkynyl-6-aryl-isothiazolo[4,3-&lt;i&gt;b&lt;/i&gt;]pyridines as Dual Inhibitors of the Lipid Kinases PIKfyve and PIP4K2C."],"pmcid":["PMC12472322"],"funding_grant_id":["R01 AI158569","1R01AI158569-01 (awards HDTRA11810039 and W81XWH2210283 and W81XWH-16-1-0691)","T32 AI007502"],"pubmed_authors":["Schols D","Einav S","Saul S","Rozenski J","Gao LJ","Persoons L","Tran DHN","Dehaen W","Martinez-Gualda B","Karim M","Kalebic D","De Jonghe S"],"additional_accession":[]},"is_claimable":false,"name":"Structure-Activity Relationship Study of 3-Alkynyl-6-aryl-isothiazolo[4,3-&lt;i&gt;b&lt;/i&gt;]pyridines as Dual Inhibitors of the Lipid Kinases PIKfyve and PIP4K2C.","description":"<b>Background/Objectives</b>: RMC-113, a 3-alkynyl-6-aryl-disubstituted isothiazolo[4,3-<i>b</i>]pyridine, is a dual inhibitor of the lipid kinases PIKfyve and PIP4K2C with broad-spectrum antiviral activity. The aim was to study the structure-activity relationship (SAR) of isothiazolo[4,3-<i>b</i>]pyridines as dual PIKfyve/PIP4K2C inhibitors. <b>Methods</b>: A series of isothiazolo[4,3-<i>b</i>]pyridines was synthesized by introducing structural variety at positions 3 and 6 of the central scaffold. The primary assay to guide the synthetic chemistry was a biochemical PIKfyve assay, with a number of analogues also tested for PIP4K2C binding affinity. Finally, isothiazolo[4,3-<i>b</i>]pyridines were also evaluated for antiviral and antitumoral activity in cell-based assays. <b>Results</b>: PI","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-05-02T03:11:21.839Z","creation":"2026-05-02T03:07:44.04Z"},"accession":"S-EPMC12472322","cross_references":{"pubmed":["41011211"],"doi":["10.3390/ph18091341"]}}