{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:18:51Z","timestamp":1791875931576,"version":"4.3.4"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.bioorg.2020.104462","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T12:51:26Z","timestamp":1604667086000},"page":"104462","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"special_numbering":"C","title":["Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)"],"prefix":"10.1016","volume":"106","author":[{"given":"Pasquale","family":"Linciano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Pinzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"Chianese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sorbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Altucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Rastelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livio","family":"Brasili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Franchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.bioorg.2020.104462_b0005","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1868-7083-4-5","article-title":"Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors","volume":"4","author":"Delcuve","year":"2012","journal-title":"Clin Epigenetics"},{"key":"10.1016\/j.bioorg.2020.104462_b0010","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1126\/science.1124000","article-title":"Histone H4\u2013K16 Acetylation Controls Chromatin Structure and Protein Interactions","volume":"311","author":"Shogren-Knaak","year":"2006","journal-title":"Sci. (Washington, DC, United States)."},{"issue":"7","key":"10.1016\/j.bioorg.2020.104462_b0015","doi-asserted-by":"crossref","first-page":"714","DOI":"10.2174\/1568026615666150825125857","article-title":"Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors","volume":"16","author":"Kim","year":"2015","journal-title":"CTMC"},{"issue":"9","key":"10.1016\/j.bioorg.2020.104462_b0020","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1158\/1078-0432.CCR-11-0767","article-title":"Molecular Pathways: Old Drugs Define New Pathways: Non-Histone Acetylation at the Crossroads of the DNA Damage Response and Autophagy","volume":"18","author":"Botrugno","year":"2012","journal-title":"Clin. Cancer Res."},{"issue":"1","key":"10.1016\/j.bioorg.2020.104462_b0025","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jmb.2004.02.006","article-title":"Molecular Evolution of the Histone Deacetylase Family: Functional Implications of Phylogenetic Analysis","volume":"338","author":"Gregoretti","year":"2004","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.bioorg.2020.104462_b0030","doi-asserted-by":"crossref","unstructured":"A.J.M. de Ruijter, A.H. van Gennip, H.N. Caron, S. Kemp, A.B.P. van Kuilenburg, Histone deacetylases (HDACs): characterization of the classical HDAC family., Biochem. J. 370 (2003) 737\u2013749. doi:10.1042\/BJ20021321.","DOI":"10.1042\/bj20021321"},{"issue":"37","key":"10.1016\/j.bioorg.2020.104462_b0035","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.1038\/sj.onc.1210620","article-title":"Histone deacetylase inhibitors: molecular mechanisms of action","volume":"26","author":"Xu","year":"2007","journal-title":"Oncogene"},{"issue":"1","key":"10.1016\/j.bioorg.2020.104462_b0040","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1172\/JCI69738","article-title":"New and emerging HDAC inhibitors for cancer treatment","volume":"124","author":"West","year":"2014","journal-title":"J. Clin. Invest."},{"issue":"37","key":"10.1016\/j.bioorg.2020.104462_b0045","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"},{"issue":"11","key":"10.1016\/j.bioorg.2020.104462_b0050","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.tins.2009.06.002","article-title":"Multiple roles of HDAC inhibition in neurodegenerative conditions","volume":"32","author":"Chuang","year":"2009","journal-title":"Trends Neurosci."},{"issue":"4","key":"10.1016\/j.bioorg.2020.104462_b0055","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/sj.cdd.4401769","article-title":"HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis","volume":"13","author":"Saha","year":"2006","journal-title":"Cell Death Differ"},{"issue":"1","key":"10.1016\/j.bioorg.2020.104462_b0060","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/icb.2011.88","article-title":"HDAC inhibitors: modulating leukocyte differentiation, survival, proliferation and inflammation","volume":"90","author":"Sweet","year":"2012","journal-title":"Immunol Cell Biol"},{"issue":"1","key":"10.1016\/j.bioorg.2020.104462_b0065","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/icb.2011.95","article-title":"HDAC inhibitors in HIV","volume":"90","author":"Wightman","year":"2012","journal-title":"Immunol Cell Biol"},{"issue":"14","key":"10.1016\/j.bioorg.2020.104462_b0070","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1074\/jbc.RA118.005185","article-title":"Histone deacetylase inhibitors induce complex host responses that contribute to differential potencies of these compounds in HIV reactivation","volume":"294","author":"Beliakova-Bethell","year":"2019","journal-title":"J. Biol. Chem."},{"issue":"10","key":"10.1016\/j.bioorg.2020.104462_b0075","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1634\/theoncologist.12-10-1247","article-title":"FDA Approval Summary: Vorinostat for Treatment of Advanced Primary Cutaneous T\u2010Cell Lymphoma","volume":"12","author":"Mann","year":"2007","journal-title":"The Oncol"},{"issue":"7","key":"10.1016\/j.bioorg.2020.104462_b0080","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1586\/era.10.88","article-title":"Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors","volume":"10","author":"Grant","year":"2010","journal-title":"Expert Rev. Anticancer Ther."},{"key":"10.1016\/j.bioorg.2020.104462_b0085","first-page":"296","article-title":"Panobinostat (Farydak): A Novel Option for the Treatment of Relapsed Or Relapsed and Refractory Multiple Myeloma","volume":"41","author":"Moore","year":"2016","journal-title":"P T."},{"issue":"10","key":"10.1016\/j.bioorg.2020.104462_b0090","doi-asserted-by":"crossref","first-page":"a026831","DOI":"10.1101\/cshperspect.a026831","article-title":"HDACs and HDAC Inhibitors in Cancer Development and Therapy","volume":"6","author":"Li","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"5","key":"10.1016\/j.bioorg.2020.104462_b0095","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/bjh.12332","article-title":"A phase II study of Givinostat in combination with hydroxycarbamide in patients with polycythaemia vera unresponsive to hydroxycarbamide monotherapy","volume":"161","author":"Finazzi","year":"2013","journal-title":"Br J Haematol"},{"issue":"5","key":"10.1016\/j.bioorg.2020.104462_b0100","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1158\/1078-0432.CCR-15-0624","article-title":"A Phase I\/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed\/Refractory Lymphoma","volume":"22","author":"Evens","year":"2016","journal-title":"Clin. Cancer Res."},{"issue":"13","key":"10.1016\/j.bioorg.2020.104462_b0105","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1158\/1078-0432.CCR-16-2526","article-title":"Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma","volume":"23","author":"Vogl","year":"2017","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.bioorg.2020.104462_b0110","doi-asserted-by":"crossref","first-page":"103679","DOI":"10.1016\/j.bioorg.2020.103679","article-title":"Discovery of specific HDAC6 inhibitor with anti-metastatic effects in pancreatic cancer cells through virtual screening and biological evaluation","volume":"97","author":"Song","year":"2020","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2020.104462_b0115","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":"10.1016\/j.bioorg.2020.104462_b0120","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ejmech.2018.07.069","article-title":"Novel spiroindoline HDAC inhibitors: Synthesis, molecular modelling and biological studies","volume":"157","author":"Brindisi","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104462_b0125","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.ejmech.2017.10.040","article-title":"Recent advances in the discovery of potent and selective HDAC6 inhibitors","volume":"143","author":"Wang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"issue":"1","key":"10.1016\/j.bioorg.2020.104462_b0130","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. Enzyme Inhib. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104462_b0135","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ejmech.2016.05.047","article-title":"Inside HDACs with more selective HDAC inhibitors","volume":"121","author":"Roche","year":"2016","journal-title":"Eur. J. Med. Chem."},{"issue":"6","key":"10.1016\/j.bioorg.2020.104462_b0140","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.drudis.2015.01.007","article-title":"Histone deacetylases: structural determinants of inhibitor selectivity","volume":"20","author":"Micelli","year":"2015","journal-title":"Drug Discovery Today"},{"issue":"13","key":"10.1016\/j.bioorg.2020.104462_b0145","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.4155\/fmc-2018-0125","article-title":"Design of selective histone deacetylase inhibitors: rethinking classical pharmacophore","volume":"10","author":"Melesina","year":"2018","journal-title":"Future Med. Chem."},{"issue":"4","key":"10.1016\/j.bioorg.2020.104462_b0150","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":"10.1016\/j.bioorg.2020.104462_b0155","doi-asserted-by":"crossref","unstructured":"A. Quotadamo, P. Linciano, P. Davoli, D. Tondi, M.P. Costi, A. Venturelli, An Improved Synthesis of CENTA, a Chromogenic Substrate for \u03b2-Lactamases, Synlett. 27 (2016) 2447\u20132450. doi:10.1055\/s-0035-1562454.","DOI":"10.1055\/s-0035-1562454"},{"issue":"24","key":"10.1016\/j.bioorg.2020.104462_b0160","doi-asserted-by":"crossref","first-page":"7662","DOI":"10.1016\/j.bmcl.2012.09.111","article-title":"Synthesis and structure\u2013activity relationships of fibrate-based analogues inside PPARs","volume":"22","author":"Giampietro","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2020.104462_b0165","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2174\/157340641001131226123613","article-title":"Effect of stilbene and chalcone scaffolds incorporation in clofibric acid on PPAR\u03b1 agonistic activity","volume":"10","author":"Giampietro","year":"2014","journal-title":"Med. Chem."},{"issue":"20","key":"10.1016\/j.bioorg.2020.104462_b0170","doi-asserted-by":"crossref","first-page":"11473","DOI":"10.1021\/acsomega.0c00559","article-title":"Design of Dual Inhibitors of Histone Deacetylase 6 and Heat Shock Protein 90","volume":"5","author":"Pinzi","year":"2020","journal-title":"ACS Omega"},{"issue":"1","key":"10.1016\/j.bioorg.2020.104462_b0175","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.molcel.2013.05.020","article-title":"Class I HDACs Share a Common Mechanism of Regulation by Inositol Phosphates","volume":"51","author":"Millard","year":"2013","journal-title":"Mol. Cell"},{"issue":"9","key":"10.1016\/j.bioorg.2020.104462_b0180","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nchembio.2134","article-title":"Histone deacetylase 6 structure and molecular basis of catalysis and inhibition","volume":"12","author":"Hai","year":"2016","journal-title":"Nat Chem Biol"},{"issue":"1","key":"10.1016\/j.bioorg.2020.104462_b0185","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1080\/14756366.2019.1613987","article-title":"Structure-based design generated novel hydroxamic acid based preferential HDAC6 lead inhibitor with on-target cytotoxic activity against primary choroid plexus carcinoma","volume":"34","author":"Kassab","year":"2019","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104462_b0190","doi-asserted-by":"crossref","unstructured":"R. Benedetti, C. Dell\u2019Aversana, T. De Marchi, D. Rotili, N.Q. Liu, B. Novakovic, S. Boccella, S. Di Maro, S. Cosconati, A. Baldi, E. Nimeus, J. Schultz, U. Hoeglund, S. Maione, C. Papulino, U. Chianese, F. Iovino, A. Federico, A. Mai, H.G. Stunnenberg, A. Nebbioso, L. Altucci, Inhibition of histone demethylases LSD1 and UTX regulates ER\u03b1 signaling in breast cancer, Cancers (Basel). 11 (2019) 2027. doi:10.3390\/cancers11122027.","DOI":"10.3390\/cancers11122027"},{"issue":"2","key":"10.1016\/j.bioorg.2020.104462_b0195","doi-asserted-by":"crossref","first-page":"886","DOI":"10.18632\/oncotarget.2816","article-title":"HDAC2 deregulation in tumorigenesis is causally connected to repression of immune modulation and defense escape","volume":"6","author":"Conte","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.bioorg.2020.104462_b0200","doi-asserted-by":"crossref","unstructured":"F. Sarno, G. Pepe, P. Termolino, V. Carafa, C. Massaro, F. Merciai, P. Campiglia, A. Nebbioso, L. Altucci, Trifolium Repens blocks proliferation in chronic myelogenous leukemia via the BCR-ABL\/STAT5 pathway, Cells. 9 (2020) 379. doi:10.3390\/cells9020379.","DOI":"10.3390\/cells9020379"},{"key":"10.1016\/j.bioorg.2020.104462_b0205","unstructured":"Schr\u00f6dinger Release 2018-3: Protein Preparation Wizard, (2018)."},{"key":"10.1016\/j.bioorg.2020.104462_b0210","unstructured":"Epike, Schr\u00f6dinger, LLC: New York, NY, (2016)."},{"key":"10.1016\/j.bioorg.2020.104462_b0215","unstructured":"Impact, Schr\u00f6dinger, LLC: New York, NY, (2016)."},{"key":"10.1016\/j.bioorg.2020.104462_b0220","unstructured":"Prime, Schr\u00f6dinger, LLC: New York, NY, (2018)."},{"issue":"1","key":"10.1016\/j.bioorg.2020.104462_b0225","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","article-title":"OPLS3: A Force Field Providing Broad Coverage of Drug-like Small Molecules and Proteins","volume":"12","author":"Harder","year":"2016","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bioorg.2020.104462_b0230","unstructured":"Schr\u00f6dinger Release 2018-3: Maestro, Schr\u00f6dinger, LLC: New York, NY, (2018)."},{"key":"10.1016\/j.bioorg.2020.104462_b0235","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jmgm.2016.09.008","article-title":"A mechanistic approach to explore novel HDAC1 inhibitor using pharmacophore modeling, 3D- QSAR analysis, molecular docking, density functional and molecular dynamics simulation study","volume":"70","author":"Choubey","year":"2016","journal-title":"J. Mol. Graph. Model."},{"key":"10.1016\/j.bioorg.2020.104462_b0240","doi-asserted-by":"crossref","unstructured":"R.A. Friesner, J.L. Banks, R.B. Murphy, T.A. Halgren, J.J. Klicic, D.T. Mainz, M.P. Repasky, E.H. Knoll, M. Shelley, J.K. Perry, D.E. Shaw, P. Francis, P.S. Shenkin, Glide: A new approach for rapid, accurate docking and scoring. 1. method and assessment of docking accuracy, J. Med. Chem. 47 (2004) 1739\u20131749. doi:10.1021\/jm0306430.","DOI":"10.1021\/jm0306430"},{"key":"10.1016\/j.bioorg.2020.104462_b0245","doi-asserted-by":"crossref","unstructured":"T.A. Halgren, R.B. Murphy, R.A. Friesner, H.S. Beard, L.L. Frye, W.T. Pollard, J.L. Banks, Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening, J. Med. Chem. 47 (2004) 1750\u20131759. doi:10.1021\/jm030644s.","DOI":"10.1021\/jm030644s"},{"key":"10.1016\/j.bioorg.2020.104462_b0250","unstructured":"Schr\u00f6dinger Release 2018-3: LigPrep, Schr\u00f6dinger LLC: New York, NY, (2018)."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206820317600?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206820317600?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:10:22Z","timestamp":1758615022000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206820317600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":50,"alternative-id":["S0045206820317600"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2020.104462","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2020.104462","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"104462"}}