{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Butler KJ"],"funding":["NIGMS NIH HHS"],"pagination":["128329"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8484043"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["50"],"pubmed_abstract":["The sphingomyelin pathway is important in cell regulation and determining cellular fate. Inhibition of sphingosine kinase isoform 1 (SK1) within this pathway, leads to a buildup of sphingosine and ceramide, two molecules directly linked to cell apoptosis, while decreasing the intracellular concentration of sphingosine-1-phosphate (S1P), a molecule linked to cellular proliferation. Recently, an inhibitor capable of inhibiting SK1 in vitro was identified, but also shown to be ineffective in vivo. A set of compounds designed to assess the impact of synthetic modifications to the hydroxynaphthalene ring region of the template inhibitor with SK1 to obtain a compound with increased efficacy in vivo. Of these fifteen compounds, 4A was shown to have an IC<sub>50</sub> = 6.55 μM with improved solub"],"journal":["Bioorganic & medicinal chemistry letters"],"pubmed_title":["Design, synthesis and analysis of novel sphingosine kinase-1 inhibitors to improve oral bioavailability."],"pmcid":["PMC8484043"],"funding_grant_id":["P20 GM103499"],"pubmed_authors":["Hair LN","Woodson SR","Wilson MR","Butler KJ","Smith MR","Walla MD","Parker EW","Turnow MT","McGlade CA","Christian Grattan T","Castro AA","Hardwick LM","Mays KM","Iacino MC","Cotham WE","Hurlbert JC","Dwyer TS","Manore SG"],"additional_accession":[]},"is_claimable":false,"name":"Design, synthesis and analysis of novel sphingosine kinase-1 inhibitors to improve oral bioavailability.","description":"The sphingomyelin pathway is important in cell regulation and determining cellular fate. Inhibition of sphingosine kinase isoform 1 (SK1) within this pathway, leads to a buildup of sphingosine and ceramide, two molecules directly linked to cell apoptosis, while decreasing the intracellular concentration of sphingosine-1-phosphate (S1P), a molecule linked to cellular proliferation. Recently, an inhibitor capable of inhibiting SK1 in vitro was identified, but also shown to be ineffective in vivo. A set of compounds designed to assess the impact of synthetic modifications to the hydroxynaphthalene ring region of the template inhibitor with SK1 to obtain a compound with increased efficacy in vivo. Of these fifteen compounds, 4A was shown to have an IC<sub>50</sub> = 6.55 μM with improved solub","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Oct","modification":"2026-05-31T16:08:07.47Z","creation":"2025-02-19T01:28:28.975Z"},"accession":"S-EPMC8484043","cross_references":{"pubmed":["34418572"],"doi":["10.1016/j.bmcl.2021.128329"]}}