{"doi":"10.1016/j.bioorg.2025.108562","title":"Design, synthesis and evaluation of structural optimization derived HDAC6 isoform-selective inhibitor","abstract":null,"journal":"Bioorganic Chemistry","year":2025,"id":633909,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":1643782,"name":"Xiaochun Ma","orcid":null,"position":1,"is_corresponding":false},{"id":1643783,"name":"Yichao Wan","orcid":null,"position":2,"is_corresponding":false},{"id":1643784,"name":"Yidong Zhong","orcid":null,"position":3,"is_corresponding":false},{"id":117238,"name":"Xuben Hou","orcid":"0000-0002-8346-9001","position":4,"is_corresponding":false},{"id":117239,"name":"Hao Fang","orcid":"0000-0002-2879-5146","position":5,"is_corresponding":false},{"id":407004,"name":"Tao Liang","orcid":"0000-0001-6355-5546","position":6,"is_corresponding":false},{"id":695486,"name":"Chen Chen","orcid":"0000-0001-5786-3956","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Design, synthesis and evaluation of structural optimization derived HDAC6 isoform-selective inhibitor","abstract":"In stark contrast to other HDAC isoforms, deletion or inhibition of HDAC6 suppresses cell proliferation without lethality or defective phenotypes, thereby establishing HDAC6 as a compelling anti-cancer target. In pursuit of safe and effective anti-cancer chemotherapy, we preformed three-round structural optimization and developed several potent HDAC6-selective inhibitors. Among these, HDSI-18 exhibited remarkable inhibitory activity (IC50 = 1.6 nM) and exceptional isoform selectivity (over 975-fold) against HDAC6. Further biological evaluations highlighted the promising properties of HDSI-18 in terms of anti-proliferative activity, mitochondrial depolarization, caspase-3 activation, apoptosis induction and druggability (both in vivo and in vitro). This study demonstrated a paradigm for the rational structural optimization of HDAC6 selective inhibitors, which may serve as a beacon for the development of more promiscuous compounds.","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40347770","pmcid":null,"openalex_id":"https://openalex.org/W4410108876","authors":[],"funders":[{"funder_name":"Scientific Research Foundation of Hunan Provincial Education Department","grant_id":"24A0358","title":null},{"funder_name":"Natural Science Foundation of Shandong Province","grant_id":"ZR2024QH497","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82404421","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"22477070","title":null}],"total_grants":4,"fwci":0.4238,"citation_percentile":0.57924701,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0045206825004420?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0045206825004420?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bioorg.2025.108562","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40347770","host_type":"repository"}],"fields_of_study":["Histone Deacetylase Inhibitors Research","Chemical Synthesis and Analysis","Peptidase Inhibition and Analysis","Histone Deacetylase 6","Histone Deacetylase Inhibitors","Humans","Drug Design","Structure-Activity Relationship","Cell Proliferation","Antineoplastic Agents","Molecular Structure","Apoptosis","Drug Screening Assays, Antitumor","Dose-Response Relationship, Drug","Animals","Cell Line, Tumor","Mice","Isoenzymes","Protein Isoforms"],"mesh_terms":["Histone Deacetylase 6","Animals","Antineoplastic Agents","Dose-Response Relationship, Drug","Drug Screening Assays, Antitumor","Humans","Isoenzymes","Structure-Activity Relationship","Drug Design","Molecular Structure","Apoptosis","Protein Isoforms","Cell Line, Tumor","Cell Proliferation","Mice","Histone Deacetylase Inhibitors"],"keywords":["Chemistry","Gene isoform","Biochemistry","Computational biology","Combinatorial chemistry","Stereochemistry","Gene","Anti-tumor","Apoptosis","HDAC6","Isoform-selective inhibitor","Structural optimization"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T12:52:01.356963Z","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":[]}