{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Schaker-Hubner L"],"funding":["Roland Ernst Stiftung"],"pagination":["e202100755"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9303312"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(9)"],"pubmed_abstract":["Herein we report the structure-activity and structure-physicochemical property relationships of a series of class I selective ortho-aminoanilides targeting the \"foot-pocket\" in HDAC1&2. To balance the structural benefits and the physicochemical disadvantages of these substances, we started with a set of HDACi related to tacedinaline (CI-994) and evaluated their solubility, lipophilicity (log D<sub>7.4</sub> ) and inhibition of selected HDAC isoforms. Subsequently, we selected the most promising \"capless\" HDACi and transferred its ZBG to our previously published scaffold featuring a peptoid-based cap group. The resulting hit compound 10 c (LSH-A54) showed favorable physicochemical properties and is a potent, selective HDAC1/2 inhibitor. The following evaluation of its slow binding properties revealed that LSH-A54 binds tightly to HDAC1 in an induced-fit mechanism. The potent HDAC1/2 inhibitory properties were reflected by attenuated cell migration in a modified wound healing assay and reduced cell viability in a clonogenic survival assay in selected breast cancer cell lines."],"journal":["ChemMedChem"],"pubmed_title":["Balancing Histone Deacetylase (HDAC) Inhibition and Drug-likeness: Biological and Physicochemical Evaluation of Class I Selective HDAC Inhibitors."],"pmcid":["PMC9303312"],"funding_grant_id":["5/19"],"pubmed_authors":["Schaker-Hubner L","Buch T","Kraft FB","Hansen FK","Haschemi R","Scholer A","Bendas G","Aigner A","Jenke R","Brumme B","Meiler J"],"additional_accession":[]},"is_claimable":false,"name":"Balancing Histone Deacetylase (HDAC) Inhibition and Drug-likeness: Biological and Physicochemical Evaluation of Class I Selective HDAC Inhibitors.","description":"Herein we report the structure-activity and structure-physicochemical property relationships of a series of class I selective ortho-aminoanilides targeting the \"foot-pocket\" in HDAC1&2. To balance the structural benefits and the physicochemical disadvantages of these substances, we started with a set of HDACi related to tacedinaline (CI-994) and evaluated their solubility, lipophilicity (log D<sub>7.4</sub> ) and inhibition of selected HDAC isoforms. Subsequently, we selected the most promising \"capless\" HDACi and transferred its ZBG to our previously published scaffold featuring a peptoid-based cap group. The resulting hit compound 10 c (LSH-A54) showed favorable physicochemical properties and is a potent, selective HDAC1/2 inhibitor. The following evaluation of its slow binding properties revealed that LSH-A54 binds tightly to HDAC1 in an induced-fit mechanism. The potent HDAC1/2 inhibitory properties were reflected by attenuated cell migration in a modified wound healing assay and reduced cell viability in a clonogenic survival assay in selected breast cancer cell lines.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2026-05-09T14:24:27.044Z","creation":"2025-04-06T19:33:53.04Z"},"accession":"S-EPMC9303312","cross_references":{"pubmed":["35073610"],"doi":["10.1002/cmdc.202100755"]}}