{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Seenadera SPD"],"funding":["CCR NIH HHS","Intramural NIH HHS","National Cancer Institute","NCI NIH HHS","Wellcome Trust"],"pagination":["1472-1476"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9465829"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(9)"],"pubmed_abstract":["Modifications at the glycolate moiety of englerin A were made to explore variations at the most sensitive site on the molecule for activity in the NCI 60 screen, wherein englerin A is highly potent and selective for renal cancer cells. Replacement of the glycolate by other functionalities as well as esterification of the glycolate hydroxyl yielded compounds which displayed excellent selectivity and potency compared with the natural product. TRPC4/5 ion channel experiments with five compounds showed delayed or reduced agonism with TRPC5, at much higher concentrations than englerin A. With TRPC4, these compounds all had no effect at 10 μM. The same compounds were not detectable in mouse serum after a single oral dose of 12.5 mg/kg. At 100 mg/kg p.o., no toxicity was observed, and blood level"],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["Biological Effects of Modifications of the Englerin A Glycolate."],"pmcid":["PMC9465829"],"funding_grant_id":["HHSN261200800001E","ZIA BC011470","ZIC SC006537","1ZICSC006537-28","HHSN261200800001C","1ZIABC011470-10","110044/Z/15/Z"],"pubmed_authors":["Strope J","Beech DJ","Figg WD","Long SA","Akee R","Peer C","Parsonage G","Parker KA","Beutler JA","Bermudez G","Seenadera SPD"],"additional_accession":[]},"is_claimable":false,"name":"Biological Effects of Modifications of the Englerin A Glycolate.","description":"Modifications at the glycolate moiety of englerin A were made to explore variations at the most sensitive site on the molecule for activity in the NCI 60 screen, wherein englerin A is highly potent and selective for renal cancer cells. Replacement of the glycolate by other functionalities as well as esterification of the glycolate hydroxyl yielded compounds which displayed excellent selectivity and potency compared with the natural product. TRPC4/5 ion channel experiments with five compounds showed delayed or reduced agonism with TRPC5, at much higher concentrations than englerin A. With TRPC4, these compounds all had no effect at 10 μM. The same compounds were not detectable in mouse serum after a single oral dose of 12.5 mg/kg. At 100 mg/kg p.o., no toxicity was observed, and blood level","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2025-04-05T12:35:23.88Z","creation":"2025-04-05T12:35:23.88Z"},"accession":"S-EPMC9465829","cross_references":{"pubmed":["36105325"],"doi":["10.1021/acsmedchemlett.2c00258"]}}