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Aberrant HDAC activity has been linked to cancer, neurodegenerative disorders, and inflammatory diseases, making these enzymes attractive therapeutic targets. HDAC inhibitors (HDACis) have gained significant attention, particularly those containing zinc-binding groups (ZBGs), which interact directly with the catalytic zinc ion in the enzyme\u2019s active site. The structural diversity of ZBGs profoundly impacts the potency, selectivity, and pharmacokinetics of HDACis. While hydroxamic acids remain the most widely used ZBGs, their limitations, such as metabolic instability and off-target effects, have driven the development of alternative scaffolds, including ortho-aminoanilides, mercaptoacetamides, alkylhydrazides, oxadiazoles, and more. This review explores the structural and mechanistic aspects of different ZBGs, their interactions with HDAC isoforms, and their influence on inhibitor selectivity. Advances in structure-based drug design have allowed the fine-tuning of HDACi pharmacophores, leading to more selective and efficacious compounds with improved drug-like properties. Understanding the nuances of ZBG interactions is essential for the rational design of next-generation HDACis, with potential applications in oncology, neuroprotection, and immunotherapy.<\/jats:p>","DOI":"10.3390\/ph18040577","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T04:05:31Z","timestamp":1744776331000},"page":"577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Drug Discovery for Histone Deacetylase Inhibition: Past, Present and Future of Zinc-Binding Groups"],"prefix":"10.3390","volume":"18","author":[{"given":"Gustavo Salgado","family":"Pires","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas (LASSBio), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal (PPGFQM), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-0598","authenticated-orcid":false,"given":"Heber Victor","family":"Tolomeu","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas (LASSBio), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Alencar","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences (PBS), Royal College of Surgeons in Ireland, 1st Floor Ardilaun House Block B, 111 St Stephen\u2019s Green, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8625-6351","authenticated-orcid":false,"given":"L\u00eddia Moreira","family":"Lima","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas (LASSBio), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal (PPGFQM), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia de F\u00e1rmacos e Medicamentos (INCT-INOFAR), Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6733-7079","authenticated-orcid":false,"given":"Carlos Alberto Manssour","family":"Fraga","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas (LASSBio), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal (PPGFQM), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia de F\u00e1rmacos e Medicamentos (INCT-INOFAR), Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4148-4243","authenticated-orcid":false,"given":"Pedro de Sena Murteira","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas (LASSBio), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal (PPGFQM), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia de F\u00e1rmacos e Medicamentos (INCT-INOFAR), Universidade Federal do Rio de Janeiro, Cidade Universit\u00e1ria, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/ije\/dyr184","article-title":"The Epigenotype","volume":"41","author":"Waddington","year":"2012","journal-title":"Int. J. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1534\/genetics.114.173492","article-title":"What Do You Mean, \u201cEpigenetic\u201d?","volume":"199","author":"Deans","year":"2015","journal-title":"Genetics"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Peixoto, P., Cartron, P.-F., Serandour, A.A., and Hervouet, E. (2020). From 1957 to Nowadays: A Brief History of Epigenetics. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207571"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cell.2007.02.006","article-title":"Epigenetics: A Landscape Takes Shape","volume":"128","author":"Goldberg","year":"2007","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1101\/gad.1787609","article-title":"An Operational Definition of Epigenetics","volume":"23","author":"Berger","year":"2009","journal-title":"Genes Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1080\/15592294.2019.1640546","article-title":"Epidrugs: Targeting Epigenetic Marks in Cancer Treatment","volume":"14","author":"Furtado","year":"2019","journal-title":"Epigenetics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bmcl.2013.11.001","article-title":"Design of Small Molecule Epigenetic Modulators","volume":"24","author":"Pachaiyappan","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1146\/annurev.cellbio.23.090506.123406","article-title":"MicroRNA Functions","volume":"23","author":"Bushati","year":"2007","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cbpa.2019.01.024","article-title":"The Roles of MicroRNAs in Epigenetic Regulation","volume":"51","author":"Yao","year":"2019","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.tig.2022.03.010","article-title":"DNA Methylation: A Historical Perspective","volume":"38","author":"Mattei","year":"2022","journal-title":"Trends Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA Methylation and Its Basic Function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1101\/gad.2037511","article-title":"CpG Islands and the Regulation of Transcription","volume":"25","author":"Deaton","year":"2011","journal-title":"Genes Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1126\/science.184.4139.868","article-title":"Chromatin Structure: A Repeating Unit of Histones and DNA","volume":"184","author":"Kornberg","year":"1974","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/38444","article-title":"Crystal Structure of the Nucleosome Core Particle at 2.8 \u00c5 Resolution","volume":"389","author":"Luger","year":"1997","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0092-8674(00)81958-3","article-title":"Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome","volume":"98","author":"Kornberg","year":"1999","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/jb\/mvx081","article-title":"Structural Diversity of the Nucleosome","volume":"163","author":"Koyama","year":"2018","journal-title":"J. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5420","DOI":"10.1038\/sj.onc.1210610","article-title":"Histone Deacetylases and Cancer","volume":"26","author":"Glozak","year":"2007","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin Modifications and Their Function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"gkae1223","DOI":"10.1093\/nar\/gkae1223","article-title":"Rapid Degradation of Histone Deacetylase 1 (HDAC1) Reveals Essential Roles in Both Gene Repression and Active Transcription","volume":"53","author":"English","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.canlet.2008.08.016","article-title":"HDAC Family: What Are the Cancer Relevant Targets?","volume":"277","author":"Witt","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrd4360","article-title":"Histone Deacetylases and Their Inhibitors in Cancer, Neurological Diseases and Immune Disorders","volume":"13","author":"Falkenberg","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/cmdc.202000934","article-title":"Strategies To Design Selective Histone Deacetylase Inhibitors","volume":"16","author":"Melesina","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12460","DOI":"10.1021\/acs.jmedchem.0c00830","article-title":"Thirty Years of HDAC Inhibitors: 2020 Insight and Hindsight","volume":"63","author":"Ho","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112887","DOI":"10.1016\/j.ejmech.2020.112887","article-title":"Mercaptoacetamide: A Promising Zinc-Binding Group for the Discovery of Selective Histone Deacetylase 6 Inhibitors","volume":"209","author":"Tavares","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jmb.2004.02.006","article-title":"V Molecular Evolution of the Histone Deacetylase Family: Functional Implications of Phylogenetic Analysis","volume":"338","author":"Gregoretti","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.2174\/1389557516666160428115959","article-title":"Beyond the Selective Inhibition of Histone Deacetylase 6","volume":"16","author":"Rodrigues","year":"2016","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e25720","DOI":"10.1002\/qua.25720","article-title":"Modeling Zinc-oxygen Coordination in Histone Deacetylase: A Comparison of Semiempirical Methods Performance","volume":"118","author":"Pinheiro","year":"2018","journal-title":"Int. J. Quantum Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/cmdc.201300413","article-title":"Towards Selective Inhibition of Histone Deacetylase Isoforms: What Has Been Achieved, Where We Are and What Will Be Next","volume":"9","author":"Thaler","year":"2014","journal-title":"ChemMedChem"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.molonc.2007.01.001","article-title":"The Role of Histone Deacetylases (HDACs) in Human Cancer","volume":"1","author":"Ropero","year":"2007","journal-title":"Mol. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrm2346","article-title":"The Rpd3\/Hda1 Family of Lysine Deacetylases: From Bacteria and Yeast to Mice and Men","volume":"9","author":"Yang","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5450","DOI":"10.1038\/sj.onc.1210613","article-title":"Class IIa Histone Deacetylases: Regulating the Regulators","volume":"26","author":"Martin","year":"2007","journal-title":"Oncogene"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1042\/bj20021321","article-title":"Histone Deacetylases (HDACs): Characterization of the Classical HDAC Family","volume":"370","author":"Ruijter","year":"2003","journal-title":"Biochem. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/417455a","article-title":"HDAC6 Is a Microtubule-Associated Deacetylase","volume":"417","author":"Hubbert","year":"2002","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.molcel.2005.04.021","article-title":"HDAC6 Regulates Hsp90 Acetylation and Chaperone-Dependent Activation of Glucocorticoid Receptor","volume":"18","author":"Kovacs","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/358169a0","article-title":"Hsp90 Chaperones Protein Folding In Vitro","volume":"358","author":"Wiech","year":"1992","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/nature04716","article-title":"Crystal Structure of an Hsp90\u2013Nucleotide\u2013P23\/Sba1 Closed Chaperone Complex","volume":"440","author":"Ali","year":"2006","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18473","DOI":"10.1074\/jbc.R800007200","article-title":"The Hsp90 Chaperone Machinery","volume":"283","author":"Wandinger","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.bbamcr.2011.09.003","article-title":"The Hsp90 Chaperone Machinery: Conformational Dynamics and Regulation by Co-Chaperones","volume":"1823","author":"Li","year":"2012","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5468","DOI":"10.1038\/sj.onc.1210614","article-title":"HDAC6, at the Crossroads between Cytoskeleton and Cell Signaling by Acetylation and Ubiquitination","volume":"26","author":"Boyault","year":"2007","journal-title":"Oncogene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/nar\/30.5.1114","article-title":"Identification of HDAC10, a Novel Class II Human Histone Deacetylase Containing a Leucine-Rich Domain","volume":"30","author":"Tong","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"25748","DOI":"10.1074\/jbc.M111871200","article-title":"Cloning and Functional Characterization of HDAC11, a Novel Member of the Human Histone Deacetylase Family","volume":"277","author":"Gao","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.sbi.2019.01.004","article-title":"Structure, Mechanism, and Inhibition of the Zinc-Dependent Histone Deacetylases","volume":"59","author":"Porter","year":"2019","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1021\/acschembio.7b00942","article-title":"Histone Deacetylase 11 Is a Fatty-Acid Deacylase","volume":"13","author":"Kutil","year":"2018","journal-title":"ACS Chem. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cell.2006.07.002","article-title":"Sirtuins in Aging and Age-Related Disease","volume":"126","author":"Longo","year":"2006","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1021\/acs.jmedchem.6b01609","article-title":"Development of 1,2,4-Oxadiazoles as Potent and Selective Inhibitors of the Human Deacetylase Sirtuin 2: Structure\u2013Activity Relationship, X-Ray Crystal Structure, and Anticancer Activity","volume":"60","author":"Moniot","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.cmet.2007.11.006","article-title":"Conserved Metabolic Regulatory Functions of Sirtuins","volume":"7","author":"Schwer","year":"2008","journal-title":"Cell Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"14015","DOI":"10.1021\/acs.jmedchem.2c01215","article-title":"Potent and Specific Activators for Mitochondrial Sirtuins Sirt3 and Sirt5","volume":"65","author":"Suenkel","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00018-022-04342-x","article-title":"SIRT7 in the Aging Process","volume":"79","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11021","DOI":"10.1074\/jbc.REV120.011438","article-title":"Biological and Catalytic Functions of Sirtuin 6 as Targets for Small-Molecule Modulators","volume":"295","author":"Klein","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.molonc.2012.09.003","article-title":"HDAC Inhibitor-based Therapies: Can We Interpret the Code?","volume":"6","author":"New","year":"2012","journal-title":"Mol. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ctrv.2005.12.006","article-title":"Histone Deacetylase Inhibitors: Multifunctional Anticancer Agents","volume":"32","author":"Liu","year":"2006","journal-title":"Cancer Treat. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.biocel.2008.07.020","article-title":"Molecular Basis of the Anti-Cancer Effects of Histone Deacetylase Inhibitors","volume":"41","author":"Epping","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.canlet.2009.02.027","article-title":"Histone Deacetylase Inhibitors as a New Weapon in the Arsenal of Differentiation Therapies of Cancer","volume":"280","author":"Botrugno","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1111\/bcp.14889","article-title":"Recent Developments of HDAC Inhibitors: Emerging Indications and Novel Molecules","volume":"87","author":"Bondarev","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1158\/1541-7786.MCR-07-0324","article-title":"Histone Deacetylase Inhibitors: Overview and Perspectives","volume":"5","author":"Dokmanovic","year":"2007","journal-title":"Mol. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrd2133","article-title":"Anticancer Activities of Histone Deacetylase Inhibitors","volume":"5","author":"Bolden","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40035-017-0089-1","article-title":"The Development Prospection of HDAC Inhibitors as a Potential Therapeutic Direction in Alzheimer\u2019s Disease","volume":"6","author":"Yang","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s13148-011-0025-7","article-title":"Targeting Huntington\u2019s Disease through Histone Deacetylases","volume":"2","author":"Gray","year":"2011","journal-title":"Clin. Epigenet."},{"key":"ref_59","first-page":"303294","article-title":"Targeting Histone Deacetylases: A Novel Approach in Parkinson\u2019s Disease","volume":"2015","author":"Sharma","year":"2015","journal-title":"Park. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"442","DOI":"10.2119\/molmed.2011.00077","article-title":"The Therapeutic Potential of HDAC Inhibitors in the Treatment of Multiple Sclerosis","volume":"17","author":"Faraco","year":"2011","journal-title":"Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1002\/med.21701","article-title":"Histone Deacetylases as Targets for the Treatment of Neurodegenerative Disorders: Challenges and Future Opportunities","volume":"40","author":"Rodrigues","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"40545","DOI":"10.1074\/jbc.M402229200","article-title":"Regulation of Histone Acetylation during Memory Formation in the Hippocampus","volume":"279","author":"Levenson","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1126\/science.1186088","article-title":"Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice","volume":"328","author":"Peleg","year":"2010","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nature05772","article-title":"Recovery of Learning and Memory Is Associated with Chromatin Remodelling","volume":"447","author":"Fischer","year":"2007","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Pelucchi, S., Stringhi, R., and Marcello, E. (2020). Dendritic Spines in Alzheimer\u2019s Disease: How the Actin Cytoskeleton Contributes to Synaptic Failure. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030908"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature07925","article-title":"HDAC2 Negatively Regulates Memory Formation and Synaptic Plasticity","volume":"459","author":"Guan","year":"2009","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6128","DOI":"10.1523\/JNEUROSCI.0296-07.2007","article-title":"Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional Activation","volume":"27","author":"Vecsey","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"43014","DOI":"10.1074\/jbc.M305905200","article-title":"Deacetylase Activity Is Required for CAMP Activation of a Subset of CREB Target Genes","volume":"278","author":"Fass","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1093\/hmg\/dds125","article-title":"Loss of HDAC6, a Novel CHIP Substrate, Alleviates Abnormal Tau Accumulation","volume":"21","author":"Cook","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"15277","DOI":"10.1074\/jbc.M117.794602","article-title":"An Acetylation\u2013Phosphorylation Switch That Regulates Tau Aggregation Propensity and Function","volume":"292","author":"Carlomagno","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.3233\/JAD-140066","article-title":"Tubastatin A\/ACY-1215 Improves Cognition in Alzheimer\u2019s Disease Transgenic Mice","volume":"41","author":"Zhang","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1750-1326-8-7","article-title":"HDAC6 as a Target for Neurodegenerative Diseases: What Makes It Different from the Other HDACs?","volume":"8","author":"Zwick","year":"2013","journal-title":"Mol. Neurodegener."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"26729","DOI":"10.1074\/jbc.C500186200","article-title":"Inhibition of Histone Deacetylase 6 Acetylates and Disrupts the Chaperone Function of Heat Shock Protein 90","volume":"280","author":"Bali","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Schapira, M. (2011). Structural Biology of Human Metal-Dependent Histone Deacetylases. Handbook of Experimental Pharmacology, Studium Press (India) Pvt. Ltd.","DOI":"10.1007\/978-3-642-21631-2_10"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.sbi.2011.08.004","article-title":"Structure, Mechanism, and Inhibition of Histone Deacetylases and Related Metalloenzymes","volume":"21","author":"Lombardi","year":"2011","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5048","DOI":"10.1021\/bi1005046","article-title":"Structures of Metal-Substituted Human Histone Deacetylase 8 Provide Mechanistic Inferences on Biological Function","volume":"49","author":"Dowling","year":"2010","journal-title":"Biochemistry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nrg2485","article-title":"The Many Roles of Histone Deacetylases in Development and Physiology: Implications for Disease and Therapy","volume":"10","author":"Haberland","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"10842","DOI":"10.1021\/ja102758v","article-title":"Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A","volume":"132","author":"Butler","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1021\/jm0303094","article-title":"Histone Deacetylase Inhibitors","volume":"46","author":"Miller","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1021\/acsmedchemlett.5b00302","article-title":"Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class IIa Histone Deacetylase (HDAC) Inhibitors","volume":"7","author":"Luckhurst","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"26926","DOI":"10.1074\/jbc.M113.490706","article-title":"Histone Deacetylase (HDAC) Inhibitor Kinetic Rate Constants Correlate with Cellular Histone Acetylation but Not Transcription and Cell Viability","volume":"288","author":"Lauffer","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1021\/acs.jmedchem.5b01478","article-title":"Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis","volume":"59","author":"Heimburg","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Simoben, C., Robaa, D., Chakrabarti, A., Schmidtkunz, K., Marek, M., Lancelot, J., Kannan, S., Melesina, J., Shaik, T., and Pierce, R. (2018). A Novel Class of Schistosoma mansoni Histone Deacetylase 8 (HDAC8) Inhibitors Identified by Structure-Based Virtual Screening and In Vitro Testing. Molecules, 23.","DOI":"10.3390\/molecules23030566"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jmgm.2015.10.006","article-title":"Homology Modeling of Parasite Histone Deacetylases to Guide the Structure-Based Design of Selective Inhibitors","volume":"62","author":"Melesina","year":"2015","journal-title":"J. Mol. Graph. Model."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"19571","DOI":"10.1039\/C9RA02985K","article-title":"Next-Generation of Selective Histone Deacetylase Inhibitors","volume":"9","author":"Yang","year":"2019","journal-title":"RSC Adv."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1021\/acschemneuro.8b00620","article-title":"CoREST Complex-Selective Histone Deacetylase Inhibitors Show Prosynaptic Effects and an Improved Safety Profile to Enable Treatment of Synaptopathies","volume":"10","author":"Fuller","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.2174\/156802612802652420","article-title":"Towards Isozyme-Selective HDAC Inhibitors for Interrogating Disease","volume":"12","author":"Gupta","year":"2012","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1016\/j.bmcl.2010.03.091","article-title":"Exploration of the HDAC2 Foot Pocket: Synthesis and SAR of Substituted N-(2-Aminophenyl)benzamides","volume":"20","author":"Bressi","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9934","DOI":"10.1021\/jm4011884","article-title":"Design, Synthesis, and Biological Evaluation of Potent and Selective Class IIa Histone Deacetylase (HDAC) Inhibitors as a Potential Therapy for Huntington\u2019s Disease","volume":"56","author":"Luckhurst","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5684","DOI":"10.1016\/j.bmcl.2009.08.010","article-title":"Diphenylmethylene Hydroxamic Acids as Selective Class IIa Histone Deacetylase Inhibitors","volume":"19","author":"Tessier","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"13459","DOI":"10.1073\/pnas.1718823114","article-title":"Unusual Zinc-Binding Mode of HDAC6-Selective Hydroxamate Inhibitors","volume":"114","author":"Porter","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4816","DOI":"10.1021\/jm400390r","article-title":"Discovery of the First Histone Deacetylase 6\/8 Dual Inhibitors","volume":"56","author":"Olson","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1021\/jm301355j","article-title":"Potent and Selective Inhibition of Histone Deacetylase 6 (HDAC6) Does Not Require a Surface-Binding Motif","volume":"56","author":"Wagner","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Yang, F., Zhao, N., Hu, Y., Jiang, C., and Zhang, H. (2020). The Development Process: From SAHA to Hydroxamate HDAC Inhibitors with Branched CAP Region and Linear Linker. Chem. Biodivers., 17.","DOI":"10.1002\/cbdv.201900427"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Osko, J.D., and Christianson, D.W. (2020). Structural Determinants of Affinity and Selectivity in the Binding of Inhibitors to Histone Deacetylase 6. Bioorg. Med. Chem. Lett., 30.","DOI":"10.1016\/j.bmcl.2020.127023"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1080\/17460441.2024.2322990","article-title":"Molecular Hybridization: A Powerful Tool for Multitarget Drug Discovery","volume":"19","author":"Franco","year":"2024","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1021\/acs.jmedchem.5b01493","article-title":"Synthesis and Biological Investigation of Oxazole Hydroxamates as Highly Selective Histone Deacetylase 6 (HDAC6) Inhibitors","volume":"59","author":"Senger","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Luo, Y., and Li, H. (2020). Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs). Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228828"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/43710","article-title":"Structures of a Histone Deacetylase Homologue Bound to the TSA and SAHA Inhibitors","volume":"401","author":"Finnin","year":"1999","journal-title":"Nature"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1021\/acs.jmedchem.0c01782","article-title":"A Review of Progress in Histone Deacetylase 6 Inhibitors Research: Structural Specificity and Functional Diversity","volume":"64","author":"Zhang","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3916","DOI":"10.1021\/acs.biochem.8b00367","article-title":"Entropy as a Driver of Selectivity for Inhibitor Binding to Histone Deacetylase 6","volume":"57","author":"Porter","year":"2018","journal-title":"Biochemistry"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.ejmech.2018.08.073","article-title":"HDAC as Onco Target: Reviewing the Synthetic Approaches with SAR Study of Their Inhibitors","volume":"158","author":"Sangwan","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1021\/jm900125m","article-title":"Design, Synthesis, and Biological Activity of Boronic Acid-Based Histone Deacetylase Inhibitors","volume":"52","author":"Suzuki","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7698","DOI":"10.1021\/acs.jmedchem.3c00226","article-title":"The Zinc-Binding Group Effect: Lessons from Non-Hydroxamic Acid Vorinostat Analogs","volume":"66","author":"Geurs","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1080\/14756366.2017.1417274","article-title":"Zinc Binding Groups for Histone Deacetylase Inhibitors","volume":"33","author":"Zhang","year":"2018","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1124\/dmd.118.082453","article-title":"The Involvement of the Mitochondrial Amidoxime Reducing Component (MARC) in the Reductive Metabolism of Hydroxamic Acids","volume":"46","author":"Ginsel","year":"2018","journal-title":"Drug Metab. Dispos."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Friedrich, A., Assmann, A.S., Schumacher, L., Stuijvenberg, J.V., Kassack, M.U., Schulz, W.A., Roos, W.P., Hansen, F.K., Pflieger, M., and Kurz, T. (2020). In Vitro Assessment of the Genotoxic Hazard of Novel Hydroxamic Acid- and Benzamide-Type Histone Deacetylase Inhibitors (HDACi). Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134747"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"21843","DOI":"10.1021\/acsomega.1c03628","article-title":"Hydroxamic Acid Derivatives: From Synthetic Strategies to Medicinal Chemistry Applications","volume":"6","author":"Citarella","year":"2021","journal-title":"ACS Omega"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4592","DOI":"10.1073\/pnas.96.8.4592","article-title":"A Synthetic Inhibitor of Histone Deacetylase, MS-27-275, with Marked In Vivo Antitumor Activity against Human Tumors","volume":"96","author":"Saito","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Fr\u00fchauf, A., and Meyer-Almes, F.-J. (2021). Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases. Molecules, 26.","DOI":"10.3390\/molecules26175151"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1021\/jm070178x","article-title":"Functional Differences in Epigenetic Modulators\u2014Superiority of Mercaptoacetamide-Based Histone Deacetylase Inhibitors Relative to Hydroxamates in Cortical Neuron Neuroprotection Studies","volume":"50","author":"Kozikowski","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1021\/acsmedchemlett.8b00487","article-title":"Molecular Basis for the Selective Inhibition of Histone Deacetylase 6 by a Mercaptoacetamide Inhibitor","volume":"9","author":"Porter","year":"2018","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.bmcl.2005.01.006","article-title":"Chemistry and Biology of Mercaptoacetamides as Novel Histone Deacetylase Inhibitors","volume":"15","author":"Chen","year":"2005","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.bmcl.2004.10.074","article-title":"Identification of a Potent Non-Hydroxamate Histone Deacetylase Inhibitor by Mechanism-Based Drug Design","volume":"15","author":"Suzuki","year":"2005","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1016\/j.jmb.2014.03.007","article-title":"Molecular Basis for the Antiparasitic Activity of a Mercaptoacetamide Derivative That Inhibits Histone Deacetylase 8 (HDAC8) from the Human Pathogen Schistosoma mansoni","volume":"426","author":"Stolfa","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"497","DOI":"10.2147\/DDDT.S237957","article-title":"Design, Synthesis and Biological Evaluation of New HDAC1 and HDAC2 Inhibitors Endowed with Ligustrazine as a Novel Cap Moiety","volume":"14","author":"Gotina","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1021\/acschembio.9b00292","article-title":"Activity-Guided Design of HDAC11-Specific Inhibitors","volume":"14","author":"Son","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"12140","DOI":"10.1021\/acs.jmedchem.2c00853","article-title":"First-in-Class Hydrazide-Based HDAC6 Selective Inhibitor with Potent Oral Anti-Inflammatory Activity by Attenuating NLRP3 Inflammasome Activation","volume":"65","author":"Yue","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1021\/acs.jmedchem.1c01472","article-title":"Potent Hydrazide-Based HDAC Inhibitors with a Superior Pharmacokinetic Profile for Efficient Treatment of Acute Myeloid Leukemia In Vivo","volume":"65","author":"Jiang","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5501","DOI":"10.1021\/acs.jmedchem.0c00442","article-title":"Design of Hydrazide-Bearing HDACIs Based on Panobinostat and Their P53 and FLT3-ITD Dependency in Antileukemia Activity","volume":"63","author":"Li","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1021\/acs.jmedchem.8b00136","article-title":"Class I HDAC Inhibitors Display Different Antitumor Mechanism in Leukemia and Prostatic Cancer Cells Depending on Their P53 Status","volume":"61","author":"Li","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"9942","DOI":"10.1021\/acs.jmedchem.6b01385","article-title":"Development of Allosteric Hydrazide-Containing Class I Histone Deacetylase Inhibitors for Use in Acute Myeloid Leukemia","volume":"59","author":"McClure","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Goracci, L., Deschamps, N., Randazzo, G.M., Petit, C., Dos Santos Passos, C., Carrupt, P.-A., Sim\u00f5es-Pires, C., and Nurisso, A. (2016). A Rational Approach for the Identification of Non-Hydroxamate HDAC6-Selective Inhibitors. Sci. Rep., 6.","DOI":"10.1038\/srep29086"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.chembiol.2014.12.015","article-title":"Identification of Histone Deacetylase Inhibitors with Benzoylhydrazide Scaffold That Selectively Inhibit Class I Histone Deacetylases","volume":"22","author":"Wang","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1080\/14756366.2020.1870457","article-title":"Discovery of Indole-3-Butyric Acid Derivatives as Potent Histone Deacetylase Inhibitors","volume":"36","author":"Chen","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"16313","DOI":"10.1021\/acs.jmedchem.2c01132","article-title":"Development of Alkylated Hydrazides as Highly Potent and Selective Class I Histone Deacetylase Inhibitors with T Cell Modulatory Properties","volume":"65","author":"Sun","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_127","unstructured":"Kim, Y., Lee, C.S., Oh, J.T., Song, H., Choi, J., and Lee, J. (2017). Oxadiazole Amine Derivative Compounds as Histone Deacetylase 6 Inhibitor, and the Pharmaceutical Composition Comprising the Same. (2017\/065473 A1), WO."},{"key":"ref_128","unstructured":"Lee, J., Han, Y., Kim, Y., Min, J., Bae, M., Kim, D., Jin, S., and Kyung, J. (2017). 1,3,4-Oxadiazole Sulfamide Derivative Compounds as Histone Deacetylase 6 Inhibitor, and the Pharmaceutical Composition Comprising the Same. (2017\/018805 A1), WO."},{"key":"ref_129","unstructured":"Ito, M., Sugiyama, H., Kubo, O., Kikuchi, F., Yasu, T., Kakegawa, K., Ikeda, Z., Miyazaki, T., Arikawa, Y., and Okawa, T. (2019). Heterocyclic Compound. (2019\/027054 A1), WO."},{"key":"ref_130","unstructured":"Lee, C.K., Ko, M.S., Yun, S.H., and Kim, H.M. (2021). 1,3,4-Oxadiazole Derivative Compounds as Histone Deacetylase 6 Inhibitor, and the Pharmaceutical Composition Comprising the Same. (2021\/210857 A1), WO."},{"key":"ref_131","unstructured":"Mandegar, M.A., Patel, S., Ding, P., Bhatt, U., Holan, M., Lee, J., Li, Y., Medina, J., Nerurkar, A., and Seidl, F. (2021). Fluoroalkyl-Oxadiazoles and Uses Thereof. (2021\/127643 A1), WO."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Cellupica, E., Gaiassi, A., Rocchio, I., Rovelli, G., Pomarico, R., Sandrone, G., Caprini, G., Cordella, P., Cukier, C., and Fossati, G. (2024). Mechanistic and Structural Insights on Difluoromethyl-1,3,4-Oxadiazole Inhibitors of HDAC6. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115885"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s42255-021-00515-3","article-title":"Histone Deacetylase 6 Inhibition Restores Leptin Sensitivity and Reduces Obesity","volume":"4","author":"Hadley","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"11087","DOI":"10.1039\/D2CC03712B","article-title":"Development of the First Non-Hydroxamate Selective HDAC6 Degraders","volume":"58","author":"Keuler","year":"2022","journal-title":"Chem. Commun."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"115907","DOI":"10.1016\/j.ejmech.2023.115907","article-title":"5-(Trifluoromethyl)-1,2,4-oxadiazole (TFMO)-Based Highly Selective Class IIa HDAC Inhibitors Exhibit Synergistic Anticancer Activity in Combination with Bortezomib","volume":"263","author":"Asfaha","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nchembio.1223","article-title":"Selective Class IIa Histone Deacetylase Inhibition via a Nonchelating Zinc-Binding Group","volume":"9","author":"Lobera","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"R3604","DOI":"10.1096\/fasebj.2022.36.S1.R3604","article-title":"A Novel Zinc Binding Group for HDAC6 Inhibition","volume":"36","author":"Cragin","year":"2022","journal-title":"FASEB J."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Ptacek, J., Snajdr, I., Schimer, J., Kutil, Z., Mikesova, J., Baranova, P., Havlinova, B., Tueckmantel, W., Majer, P., and Kozikowski, A. (2023). Selectivity of Hydroxamate- and Difluoromethyloxadiazole-Based Inhibitors of Histone Deacetylase 6 In Vitro and in Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054720"},{"key":"ref_139","unstructured":"Yates, C.M. (2019). Metalloenzyme Inhibitor Compounds. (2018\/0256572 A1), U.S. Patent."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Cellupica, E., Caprini, G., Cordella, P., Cukier, C., Fossati, G., Marchini, M., Rocchio, I., Sandrone, G., Vanoni, M.A., and Vergani, B. (2023). Difluoromethyl-1,3,4-Oxadiazoles Are Slow-Binding Substrate Analog Inhibitors of Histone Deacetylase 6 with Unprecedented Isotype Selectivity. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2022.102800"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"13821","DOI":"10.1021\/acs.jmedchem.3c01345","article-title":"Difluoromethyl-1,3,4-Oxadiazoles Are Selective, Mechanism-Based, and Essentially Irreversible Inhibitors of Histone Deacetylase","volume":"66","author":"Watson","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1016\/j.apsb.2022.03.009","article-title":"Recent Advances in the Translation of Drug Metabolism and Pharmacokinetics Science for Drug Discovery and Development","volume":"12","author":"Lai","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Pillpe-Meza, R.M., Gouveia, W.L., Barbosa, G., Fraga, C.A.M., Barreiro, E.J., and Lima, L.M. (2024). Cytotoxic and Antiproliferative Activity of LASSBio-2208 and the Attempts to Determine Its Drug Metabolism and Pharmacokinetics In Vitro Profile. Pharmaceuticals, 17.","DOI":"10.20944\/preprints202402.0866.v1"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s40265-014-0275-8","article-title":"Belinostat: First Global Approval","volume":"74","author":"Poole","year":"2014","journal-title":"Drugs"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jpba.2013.03.025","article-title":"LC\u2013MS\/MS Assay for the Quantitation of the HDAC Inhibitor Belinostat and Five Major Metabolites in Human Plasma","volume":"81","author":"Kiesel","year":"2013","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s10637-015-0321-8","article-title":"Pharmacokinetics, Metabolism, and Excretion of 14C-Labeled Belinostat in Patients with Recurrent or Progressive Malignancies","volume":"34","author":"Calvo","year":"2016","journal-title":"Investig. New Drugs"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s00280-016-3167-7","article-title":"A Phase I Study to Determine the Pharmacokinetics and Urinary Excretion of Belinostat and Metabolites in Patients with Advanced Solid Tumors","volume":"78","author":"Bailey","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1158\/1078-0432.CCR-07-1786","article-title":"A Phase 1 Pharmacokinetic and Pharmacodynamic Study of the Histone Deacetylase Inhibitor Belinostat in Patients with Advanced Solid Tumors","volume":"14","author":"Steele","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s00280-010-1419-5","article-title":"Pharmacokinetic and Pharmacodynamic Properties of an Oral Formulation of the Histone Deacetylase Inhibitor Belinostat (PXD101)","volume":"67","author":"Steele","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Wang, L.-Z., Ram\u00c3rez, J., Yeo, W., Chan, M.-Y.M., Thuya, W.-L., Lau, J.-Y.A., Wan, S.-C., Wong, A.L.-A., Zee, Y.-K., and Lim, R. (2014). Correction: Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients. PLoS ONE, 9.","DOI":"10.1371\/annotation\/df796504-a2ea-4807-a412-85985bb2550b"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Zhang, C., Guo, S., Zhong, Q., Zhang, Q., Hossain, A., Zheng, S., and Wang, G. (2019). Metabolism and Pharmacokinetic Study of the Boron-Containing Prodrug of Belinostat (ZL277), a Pan HDAC Inhibitor with Enhanced Bioavailability. Pharmaceuticals, 12.","DOI":"10.3390\/ph12040180"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"115915","DOI":"10.1016\/j.ejmech.2023.115915","article-title":"Discovery of Benzamide-Based PI3K\/HDAC Dual Inhibitors with Marked Pro-Apoptosis Activity in Lymphoma Cells","volume":"262","author":"Deng","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1200\/JCO.2005.02.188","article-title":"Phase I and Pharmacokinetic Study of MS-275, a Histone Deacetylase Inhibitor, in Patients with Advanced and Refractory Solid Tumors or Lymphoma","volume":"23","author":"Ryan","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1021\/jm901830p","article-title":"Bis(morpholino-1,3,5-triazine) Derivatives: Potent Adenosine 5\u2032-Triphosphate Competitive Phosphatidylinositol-3-kinase\/Mammalian Target of Rapamycin Inhibitors: Discovery of Compound 26 (PKI-587), a Highly Efficacious Dual Inhibitor","volume":"53","author":"Venkatesan","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2174\/187231207780363642","article-title":"Disposition of Vorinostat, A Novel Histone Deacetylase Inhibitor and Anticancer Agent, in Preclinical Species","volume":"1","author":"Sandhu","year":"2007","journal-title":"Drug Metab. Lett."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1021\/acsmedchemlett.0c00532","article-title":"Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington\u2019s Disease","volume":"12","author":"Stott","year":"2021","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1002\/cncr.34974","article-title":"Recent Histone Deacetylase Inhibitors in Cancer Therapy","volume":"129","author":"Parveen","year":"2023","journal-title":"Cancer"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Sun, Y., Hong, J.H., Ning, Z., Pan, D., Fu, X., Lu, X., and Tan, J. (2022). Therapeutic Potential of Tucidinostat, a Subtype-Selective HDAC Inhibitor, in Cancer Treatment. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.932914"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S1474-4422(24)00036-X","article-title":"Safety and Efficacy of Givinostat in Boys with Duchenne Muscular Dystrophy (EPIDYS): A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial","volume":"23","author":"Mercuri","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-021-00248-3","article-title":"Duchenne Muscular Dystrophy","volume":"7","author":"Duan","year":"2021","journal-title":"Nat. Rev. Dis. 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