{"doi":"10.1002/cmdc.201402371","title":"Identification of Structural Features of 2‐Alkylidene‐1,3‐Dicarbonyl Derivatives that Induce Inhibition and/or Activation of Histone Acetyltransferases KAT3B/p300 and KAT2B/PCAF","abstract":"<jats:title>Abstract</jats:title><jats:p>Dysregulation of the activity of lysine acetyltransferases (KATs) is related to a variety of diseases and/or pathological cellular states; however, their role remains unclear. Therefore, the development of selective modulators of these enzymes is of paramount importance, because these molecules could be invaluable tools for assessing the importance of KATs in several pathologies. We recently found that diethyl pentadecylidenemalonate (SPV106) possesses a previously unobserved inhibitor/activator activity profile against protein acetyltransferases. Herein, we report that manipulation of the carbonyl functions of a series of analogues of SPV106 yielded different activity profiles against KAT2B and KAT3B (pure KAT2B activator, pan‐inhibitor, or mixed KAT2B activator/KAT3B inhibitor). Among the novel compounds, a few derivatives may be useful chemical tools for studying the mechanism of lysine acetylation and its implications in physiological and/or pathological processes.</jats:p>","journal":"ChemMedChem","year":2015,"id":14672,"datarank":0.9160526880321957,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.4058730807828723,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.4058730807828723,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":19,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":114880,"name":"Ciro Milite","orcid":null,"position":1,"is_corresponding":false},{"id":114881,"name":"Alessandra Feoli","orcid":null,"position":2,"is_corresponding":false},{"id":114882,"name":"Monica Viviano","orcid":null,"position":3,"is_corresponding":false},{"id":111037,"name":"Antonello Mai","orcid":"0000-0001-9176-2382","position":4,"is_corresponding":false},{"id":114883,"name":"Ettore Novellino","orcid":null,"position":5,"is_corresponding":false},{"id":114884,"name":"Alessandra Tosco","orcid":null,"position":6,"is_corresponding":false},{"id":114684,"name":"Gianluca Sbardella","orcid":null,"position":7,"is_corresponding":false},{"id":114879,"name":"Sabrina Castellano","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25333655","pmcid":null,"openalex_id":"https://openalex.org/W2079116818","authors":[],"funders":[{"funder_name":"European Commission","grant_id":"282510","title":"A BLUEPRINT of Haematopoietic Epigenomes"}],"total_grants":1,"fwci":1.4226,"citation_percentile":0.81139499,"influential_citations":0,"citation_trend":[{"year":2015,"count":3},{"year":2016,"count":5},{"year":2017,"count":2},{"year":2018,"count":2},{"year":2019,"count":5},{"year":2020,"count":4},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2024,"count":3},{"year":2025,"count":3}],"oa_status":"closed","license":"Wiley Online Library User Agreement","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcmdc.201402371","host_type":"publisher"},{"url":"https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/cmdc.201402371","host_type":"publisher"},{"url":"https://doi.org/10.1002/cmdc.201402371","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25333655","host_type":"repository"},{"url":"http://hdl.handle.net/11573/884227","host_type":"repository"},{"url":"https://dx.doi.org/10.1002/cmdc.201402371","host_type":""},{"url":"https://hdl.handle.net/11386/4485257","host_type":""},{"url":"https://hdl.handle.net/11573/884227","host_type":""},{"url":"http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1860-7187","host_type":""},{"url":"http://dx.doi.org/10.1002/cmdc.201402371","host_type":""}],"fields_of_study":["Histone Deacetylase Inhibitors Research","Protein Degradation and Inhibitors","Ubiquitin and proteasome pathways","Chemistry","Medicine","0301 basic medicine","0303 health sciences","03 medical and health sciences","Acetylation","Cell Line, Tumor","Cell Survival","E1A-Associated p300 Protein","Enzyme Inhibitors","HeLa Cells","Histones","Humans","Phylogeny","Protein Binding","Structure-Activity Relationship","Surface Plasmon Resonance","p300-CBP Transcription Factors","p300-CBP-Associated Factor"],"mesh_terms":["p300-CBP-Associated Factor","Acetylation","Cell Survival","Enzyme Inhibitors","HeLa Cells","Histones","Humans","Phylogeny","Protein Binding","Structure-Activity Relationship","Surface Plasmon Resonance","Cell Line, Tumor","p300-CBP Transcription Factors","E1A-Associated p300 Protein","Hela Cells"],"keywords":["PCAF","Histone Acetyltransferases","Acetyltransferases","Histone","Acetylation","Chemistry","P300-CBP Transcription Factors","Identification (biology)","Histone acetyltransferase","Biochemistry","Cancer research","Computational biology","Stereochemistry","Cell biology","Molecular biology","Biology","Gene","Surface plasmon resonance","Structure-activity relationships","Epigenetics","Pcaf Activators","Lysine Acetyltransferases","epigenetics; lysine acetyltransferases; PCAF activators; structure-activity relationships; surface plasmon resonance; acetylation; cell line, tumor; cell survival; E1A-associated p300 protein; enzyme inhibitors; HeLa cells; histones; humans; phylogeny; protein binding; structure-activity relationship; surface plasmon resonance; p300-CBP transcription factors; pharmacology, toxicology and pharmaceutics (all); organic chemistry; molecular medicine; medicine (all)","Cell Survival","p300-CBP-Associated Factor","Histones","Structure-Activity Relationship","Cell Line, Tumor","Humans","epigenetics; lysine acetyltransferases (KATs); PCAF activators; structure-activity relationships; surface plasmon resonance","Enzyme Inhibitors","E1A-Associated p300 Protein","Phylogeny","HeLa Cells","Protein Binding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T13:37:42.123492Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}