{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lecointre B"],"funding":["INSERM","the European Union's Seventh Framework Programme for Research, Technological Development and Demonstration","La Ligue Contre le Cancer"],"pagination":["20170364"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5915728"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["373(1748)"],"pubmed_abstract":["A series of hydroxamic acids linked by different lengths to a chiral imidazo-ketopiperazine scaffold were synthesized. The compounds with linker lengths of 6 and 7 carbon atoms were the most potent in histone deacetylase (HDAC) inhibition, and were specific submicromolar inhibitors of the HDAC1, HDAC6 and HDAC8 isoforms. A docking model for the binding mode predicts binding of the hydroxamic acid to the active site zinc cation and additional interactions between the imidazo-ketopiperazine and the enzyme rim. The compounds were micromolar inhibitors of the MV4-11, THP-1 and U937 cancer cell lines. Increased levels of histone H3 and tubulin acetylation support a cellular mechanism of action through HDAC inhibition.This article is part of a discussion meeting issue 'Frontiers in epigenetic ch"],"journal":["Philosophical transactions of the Royal Society of London. Series B, Biological sciences"],"pubmed_title":["Isoform-selective HDAC1/6/8 inhibitors with an imidazo-ketopiperazine cap containing stereochemical diversity."],"pmcid":["PMC5915728"],"funding_grant_id":["241865 (SEtTReND) and 602080 (A-ParaDDisE)"],"pubmed_authors":["Narozny R","Romier C","Borrello MT","Senger J","Ganesan A","Melesina J","Marek M","Chakrabarti A","Jung M","Lecointre B","Sippl W","Bischoff L"],"additional_accession":[]},"is_claimable":false,"name":"Isoform-selective HDAC1/6/8 inhibitors with an imidazo-ketopiperazine cap containing stereochemical diversity.","description":"A series of hydroxamic acids linked by different lengths to a chiral imidazo-ketopiperazine scaffold were synthesized. The compounds with linker lengths of 6 and 7 carbon atoms were the most potent in histone deacetylase (HDAC) inhibition, and were specific submicromolar inhibitors of the HDAC1, HDAC6 and HDAC8 isoforms. A docking model for the binding mode predicts binding of the hydroxamic acid to the active site zinc cation and additional interactions between the imidazo-ketopiperazine and the enzyme rim. The compounds were micromolar inhibitors of the MV4-11, THP-1 and U937 cancer cell lines. Increased levels of histone H3 and tubulin acetylation support a cellular mechanism of action through HDAC inhibition.This article is part of a discussion meeting issue 'Frontiers in epigenetic ch","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Jun","modification":"2026-05-01T01:55:11.905Z","creation":"2026-04-07T16:34:12.668Z"},"accession":"S-EPMC5915728","cross_references":{"pubmed":["29685969"],"doi":["10.1098/rstb.2017.0364"]}}