{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:55:51Z","timestamp":1772772951456,"version":"3.50.1"},"reference-count":69,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","award":["100343060"],"award-info":[{"award-number":["100343060"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The degree of acetylation of lysine residues on histones influences the accessibility of DNA and, furthermore, the gene expression. Histone deacetylases (HDACs) are overexpressed in various tumour diseases, resulting in the interest in HDAC inhibitors for cancer therapy. The aim of this work is the development of a novel 18F-labelled HDAC1\/2-specific inhibitor with a benzamide-based zinc-binding group to visualize these enzymes in brain tumours by positron emission tomography (PET). BA3, exhibiting high inhibitory potency for HDAC1 (IC50 = 4.8 nM) and HDAC2 (IC50 = 39.9 nM), and specificity towards HDAC3 and HDAC6 (specificity ratios &gt;230 and &gt;2080, respectively), was selected for radiofluorination. The two-step one-pot radiosynthesis of [18F]BA3 was performed in a TRACERlab FX2 N radiosynthesizer by a nucleophilic aliphatic substitution reaction. The automated radiosynthesis of [18F]BA3 resulted in a radiochemical yield of 1%, a radiochemical purity of &gt;96% and a molar activity between 21 and 51 GBq\/\u00b5mol (n = 5, EOS). For the characterization of BA3, in vitro and in vivo experiments were carried out. The results of these pharmacological and pharmacokinetic studies indicate a suitable inhibitory potency of BA3, whereas the applicability for non-invasive imaging of HDAC1\/2 by PET requires further optimization of the properties of this compound.<\/jats:p>","DOI":"10.3390\/ph15030324","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T01:53:54Z","timestamp":1646790834000},"page":"324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development and Biological Evaluation of the First Highly Potent and Specific Benzamide-Based Radiotracer [18F]BA3 for Imaging of Histone Deacetylases 1 and 2 in Brain"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5067-4845","authenticated-orcid":false,"given":"Oliver","family":"Clau\u00df","sequence":"first","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7734-124X","authenticated-orcid":false,"given":"Linda","family":"Sch\u00e4ker-H\u00fcbner","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany"},{"name":"Institute for Drug Discovery, Medical Faculty, Leipzig University, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7390-3575","authenticated-orcid":false,"given":"Barbara","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1136-3857","authenticated-orcid":false,"given":"Magali","family":"Toussaint","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-3062","authenticated-orcid":false,"given":"Winnie","family":"Deuther-Conrad","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-2325","authenticated-orcid":false,"given":"Daniel","family":"G\u00fcndel","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Teodoro","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sladjana","family":"Duki\u0107-Stefanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4358-5171","authenticated-orcid":false,"given":"Friedrich-Alexander","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4846-1271","authenticated-orcid":false,"given":"Klaus","family":"Kopka","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"},{"name":"Faculty of Chemistry and Food Chemistry, School of Science, Technical University Dresden, 01062 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5555-7058","authenticated-orcid":false,"given":"Peter","family":"Brust","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-5975","authenticated-orcid":false,"given":"Finn K.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Scheunemann","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tago, T., and Toyohara, J. (2018). Advances in the Development of PET Ligands Targeting Histone Deacetylases for the Assessment of Neurodegenerative Diseases. Molecules, 23.","DOI":"10.3390\/molecules23020300"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1200\/JCO.2009.22.1291","article-title":"Histone deacetylase inhibitors in cancer therapy","volume":"27","author":"Lane","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_3","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."},{"key":"ref_4","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. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1615\/CritRevOncog.2015012997","article-title":"Histone deacetylases and mechanisms of regulation of gene expression","volume":"20","author":"Chen","year":"2015","journal-title":"Crit. Rev. Oncog."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6936","DOI":"10.1021\/jm0505011","article-title":"Toward selective histone deacetylase inhibitor design: Homology modeling, docking studies, and molecular dynamics simulations of human class I histone deacetylases","volume":"48","author":"Wang","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"576946","DOI":"10.3389\/fcell.2020.576946","article-title":"The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy","volume":"8","author":"Li","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1038\/s41467-020-17078-8","article-title":"The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure","volume":"11","author":"Turnbull","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"48027","DOI":"10.18632\/oncotarget.18227","article-title":"Knockdown of HDAC1 expression suppresses invasion and induces apoptosis in glioma cells","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18577","DOI":"10.18632\/oncotarget.14612","article-title":"Advances in epigenetic glioblastoma therapy","volume":"8","author":"Lee","year":"2017","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3389\/fphar.2020.00537","article-title":"Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation","volume":"11","author":"Shukla","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Jenke, R., Ressing, N., Hansen, F.K., Aigner, A., and Buch, T. (2021). Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives. Cancers, 13.","DOI":"10.3390\/cancers13040634"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107721","DOI":"10.1016\/j.pharmthera.2020.107721","article-title":"Targeting post-translational histone modifying enzymes in glioblastoma","volume":"220","author":"Kunadis","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1158\/0008-5472.CAN-03-2630","article-title":"Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275","volume":"64","author":"Camphausen","year":"2004","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6066","DOI":"10.1158\/1078-0432.CCR-04-0537","article-title":"Enhancement of xenograft tumor radiosensitivity by the histone deacetylase inhibitor MS-275 and correlation with histone hyperacetylation","volume":"10","author":"Camphausen","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_18","first-page":"1004","article-title":"VorinostatSAHA Promotes Hyper-Radiosensitivity in Wild Type p53 Human Glioblastoma Cells","volume":"2","author":"Diss","year":"2014","journal-title":"JSM Clin. Oncol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1021\/jm200620f","article-title":"In vivo PET imaging of histone deacetylases by 18F-suberoylanilide hydroxamic acid (18F-SAHA)","volume":"54","author":"Hendricks","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1002\/jlcr.1122","article-title":"Radiosynthesis of 6-([18F]fluoroacetamido)-1-hexanoicanilide ([18F]FAHA) for PET imaging of histone deacetylase (HDAC)","volume":"49","author":"Mukhopadhyay","year":"2006","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.nucmedbio.2008.12.005","article-title":"Evaluation of 6-([18F]fluoroacetamido)-1-hexanoicanilide for PET imaging of histone deacetylase in the baboon brain","volume":"36","author":"Reid","year":"2009","journal-title":"Nucl. Med. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.neuroimage.2012.09.019","article-title":"Imaging epigenetic regulation by histone deacetylases in the brain using PET\/MRI with 18F-FAHA","volume":"64","author":"Yeh","year":"2013","journal-title":"Neuroimage"},{"key":"ref_23","first-page":"978814","article-title":"Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model","volume":"9788","author":"Li","year":"2016","journal-title":"SPIE Med. Imaging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3612027","DOI":"10.1155\/2018\/3612027","article-title":"In Vivo 6-([18F]Fluoroacetamido)-1-hexanoicanilide PET Imaging of Altered Histone Deacetylase Activity in Chemotherapy-Induced Neurotoxicity","volume":"2018","author":"Fukumitsu","year":"2018","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6660358","DOI":"10.1155\/2021\/6660358","article-title":"In Vivo Evaluation of the Combined Anticancer Effects of Cisplatin and SAHA in Nonsmall Cell Lung Carcinoma Using [18F]FAHA and [18F]FDG PET\/CT Imaging","volume":"2021","author":"Yeh","year":"2021","journal-title":"Mol. Imaging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/nbt1272","article-title":"Dimethyl sulfoxide to vorinostat: Development of this histone deacetylase inhibitor as an anticancer drug","volume":"25","author":"Marks","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7999","DOI":"10.1021\/jm500872p","article-title":"In vivo imaging of histone deacetylases (HDACs) in the central nervous system and major peripheral organs","volume":"57","author":"Wang","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1021\/cn500162j","article-title":"PET imaging demonstrates histone deacetylase target engagement and clarifies brain penetrance of known and novel small molecule inhibitors in rat","volume":"5","author":"Schroeder","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1021\/acschemneuro.5b00066","article-title":"Kinetic Analysis and Quantification of [11C]Martinostat for in Vivo HDAC Imaging of the Brain","volume":"6","author":"Wey","year":"2015","journal-title":"ACS Chem. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"351ra106","DOI":"10.1126\/scitranslmed.aaf7551","article-title":"Insights into neuroepigenetics through human histone deacetylase PET imaging","volume":"8","author":"Wey","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_31","first-page":"4704","article-title":"Mutagenicity of Hydroxamic Acids and the Probable Involvement of Carbamoylation","volume":"40","author":"Skipper","year":"1980","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.3390\/ph3092751","article-title":"Clinical Toxicities of Histone Deacetylase Inhibitors","volume":"3","author":"Subramanian","year":"2010","journal-title":"Pharmaceuticals"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/cmdc.201500486","article-title":"Why Hydroxamates May Not Be the Best Histone Deacetylase Inhibitors\u2014What Some May Have Forgotten or Would Rather Forget?","volume":"11","author":"Shen","year":"2016","journal-title":"ChemMedChem"},{"key":"ref_34","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":"ref_35","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1021\/cn500021p","article-title":"Image-guided synthesis reveals potent blood-brain barrier permeable histone deacetylase inhibitors","volume":"5","author":"Seo","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1021\/cn9000268","article-title":"Histone deacetylase inhibitor, MS-275, exhibits poor brain penetration: PK studies of [11C]MS-275 using Positron Emission Tomography","volume":"1","author":"Hooker","year":"2010","journal-title":"ACS Chem. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.1021\/jm701079h","article-title":"Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity","volume":"50","author":"Moradei","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.bmcl.2007.12.031","article-title":"Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1\/HDAC2 inhibitors (SHI-1:2)","volume":"18","author":"Methot","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1021\/jm7011408","article-title":"Histone deacetylase inhibitors: From bench to clinic","volume":"51","author":"Paris","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1021\/jm401837e","article-title":"Mutagenesis studies of the 14 A internal cavity of histone deacetylase 1: Insights toward the acetate-escape hypothesis and selective inhibitor design","volume":"57","author":"Wambua","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0969-8051(94)90012-4","article-title":"18F-labelled vesamicol derivatives: Syntheses and preliminary in vivo small animal positron emission tomography evaluation","volume":"21","author":"Rogers","year":"1994","journal-title":"Nucl. Med. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.nucmedbio.2007.10.004","article-title":"A new 18F-labeled fluoroacetylmorpholino derivative of vesamicol for neuroimaging of the vesicular acetylcholine transporter","volume":"35","author":"Sorger","year":"2008","journal-title":"Nucl. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.nucmedbio.2013.06.006","article-title":"Synthesis and biological evaluation of N-(2-[(18)F]Fluoropropionyl)-L-methionine for tumor imaging","volume":"40","author":"Hu","year":"2013","journal-title":"Nucl. Med. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hu, K., Tang, X., Tang, G., Yao, S., Yao, B., Wang, H., Nie, D., Liang, X., Tang, C., and He, S. (2015). 18F-FP-PEG2-beta-Glu-RGD2: A Symmetric Integrin alphavbeta3-Targeting Radiotracer for Tumor PET Imaging. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138675"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"34100","DOI":"10.18632\/oncotarget.9115","article-title":"Radiosynthesis and preliminary biological evaluation of N-(2-[18F]fluoropropionyl)-L-glutamine as a PET tracer for tumor imaging","volume":"7","author":"Tang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.nucmedbio.2021.02.002","article-title":"Radiosynthesis and evaluation of N(5)-(2-(18)F-fluoropropanyl) ornithine as a potential agent for tumor PET imaging","volume":"94\u201395","author":"Wang","year":"2021","journal-title":"Nucl. Med. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1021\/ml5002932","article-title":"1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain","volume":"5","author":"Demont","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1021\/ml4004233","article-title":"Delayed and Prolonged Histone Hyperacetylation with a Selective HDAC1\/HDAC2 Inhibitor","volume":"5","author":"Methot","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.bmcl.2007.11.047","article-title":"Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2)","volume":"18","author":"Witter","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ejmech.2017.03.069","article-title":"Selective HDAC inhibitors with potent oral activity against leukemia and colorectal cancer: Design, structure-activity relationship and anti-tumor activity study","volume":"134","author":"Li","year":"2017","journal-title":"Eur. J. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1016\/j.bmc.2017.03.036","article-title":"Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups","volume":"25","author":"Gao","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/bkcs.12254","article-title":"Design and Synthesis of Novel N-(2-aminophenyl)benzamide Derivatives as Histone Deacetylase Inhibitors and Their Antitumor Activity Study","volume":"42","author":"La","year":"2021","journal-title":"Bull. Korean Chem. Soc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7188","DOI":"10.1021\/acs.jmedchem.6b00709","article-title":"Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening","volume":"59","author":"Kilchmann","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Sch\u00e4ker-H\u00fcbner, L., Haschemi, R., B\u00fcch, T., Kraft, F.B., Brumme, B., Sch\u00f6ler, A., Jenke, R., Meiler, J., Aigner, A., and Bendas, G. (2022). Balancing Histone Deacetylase (HDAC) Inhibition and Drug-likeness: Biological and Physicochemical Evaluation of Class I Selective HDAC Inhibitors. ChemMedChem, e202100755.","DOI":"10.1002\/cmdc.202100755"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1021\/acsptsci.1c00133","article-title":"Insights into Elution of Anion Exchange Cartridges: Opening the Path toward Aliphatic (18)F-Radiolabeling of Base-Sensitive Tracers","volume":"4","author":"Bratteby","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1021\/jo00191a035","article-title":"Anhydrous Tetrabutylammonium Fluoride\u2014A Mild but Highly Efficient Source of Nucleophilic Fluoride-Ion","volume":"49","author":"Cox","year":"1984","journal-title":"J. Org. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.tips.2009.05.005","article-title":"PET radiotracers: Crossing the blood-brain barrier and surviving metabolism","volume":"30","author":"Pike","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3109\/10611869808997889","article-title":"Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors","volume":"6","author":"Camenisch","year":"1998","journal-title":"J. Drug Target."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.mibio.2003.09.014","article-title":"Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents","volume":"5","author":"Waterhouse","year":"2003","journal-title":"Mol. Imaging Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Lindemann, M., Moldovan, R.P., Hinz, S., Deuther-Conrad, W., Gundel, D., Dukic-Stefanovic, S., Toussaint, M., Teodoro, R., Juhl, C., and Steinbach, J. (2020). Development of a Radiofluorinated Adenosine A2B Receptor Antagonist as Potential Ligand for PET Imaging. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093197"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"a018713","DOI":"10.1101\/cshperspect.a018713","article-title":"Erasers of histone acetylation: The histone deacetylase enzymes","volume":"6","author":"Seto","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1021\/acsmedchemlett.8b00099","article-title":"Design, Synthesis, and Blood-Brain Barrier Transport Study of Pyrilamine Derivatives as Histone Deacetylase Inhibitors","volume":"9","author":"Hiranaka","year":"2018","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_64","first-page":"889","article-title":"Some properties of \u03b1-fluoronitriles","volume":"36","author":"Yakubovich","year":"1966","journal-title":"J. Gen. Chem. USSR"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0022-1139(99)00284-5","article-title":"The enzymatic resolution of an \u03b1-fluoroamide by an acylase","volume":"102","author":"Banks","year":"2000","journal-title":"J. Fluor. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.apradiso.2015.03.009","article-title":"Convenient recycling and reuse of bombarded [18O]H2O for the production and the application of [18F]F\u2212","volume":"101","author":"Rotering","year":"2015","journal-title":"Appl. Radiat. Isot."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1016\/j.bmc.2018.07.045","article-title":"Radiosynthesis and in vivo evaluation of a fluorine-18 labeled pyrazine based radioligand for PET imaging of the adenosine A2B receptor","volume":"26","author":"Lindemann","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"14620","DOI":"10.1021\/acs.jmedchem.1c01119","article-title":"4-Acyl Pyrrole Capped HDAC Inhibitors: A New Scaffold for Hybrid Inhibitors of BET Proteins and Histone Deacetylases as Antileukemia Drug Leads","volume":"64","author":"Warstat","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S0003-2697(03)00276-8","article-title":"Nonisotopic substrate for assaying both human zinc and NAD+-dependent histone deacetylases","volume":"319","author":"Heltweg","year":"2003","journal-title":"Anal. Biochem."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/3\/324\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:34:05Z","timestamp":1760135645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/3\/324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":69,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ph15030324"],"URL":"https:\/\/doi.org\/10.3390\/ph15030324","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]}}}