{"doi":"10.1016/j.bbrc.2009.06.113","title":"Identification of a small molecule SIRT2 inhibitor with selective tumor cytotoxicity","abstract":null,"journal":"Biochemical and Biophysical Research Communications","year":2009,"id":679552,"datarank":0.6698862177981877,"base_score":4.465908118654584,"endowment":4.465908118654584,"self_citation_contribution":0.6698862177981877,"citation_network_contribution":0.0,"self_endowment_contribution":0.6698862177981877,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":86,"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":1067371,"name":"Qingyan Au","orcid":"0009-0009-0925-1766","position":1,"is_corresponding":false},{"id":1775503,"name":"Menghua Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":1775504,"name":"Jack R. Barber","orcid":null,"position":3,"is_corresponding":false},{"id":1775506,"name":"Shi Chung Ng","orcid":null,"position":4,"is_corresponding":false},{"id":4392,"name":"Bin Zhang","orcid":"0000-0002-4579-1075","position":5,"is_corresponding":false},{"id":1775502,"name":"Yingjia Zhang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Identification of a small molecule SIRT2 inhibitor with selective tumor cytotoxicity","abstract":"As a member of the class III histone deacetylases, Sirtuin-2 (SIRT2) is critical in cell cycle regulation which makes it a potential target for cancer therapeutics. In this study, we identified a novel SIRT2 inhibitor, AC-93253, with IC(50) of 6 microM in vitro. The compound is selective, inhibiting SIRT2 7.5- and 4-fold more potently than the closely related SIRT1 and SIRT3, respectively. AC-93253 significantly enhanced acetylation of tubulin, p53, and histone H4, confirming SIRT2 and SIRT1 as its cellular targets. AC-93253 as a single agent exhibited submicromolar selective cytotoxicity towards all four tumor cell lines tested with a therapeutic window up to 200-fold, comparing to any of the three normal cell types tested. Results from high content analysis suggested that AC-93253 significantly triggered apoptosis. Taken together, SIRT2 selective inhibitor AC-93253 may serve as a novel chemical scaffold for structure-activity relationship study and future lead development.","is_dataset_classified":null,"base_score":4.465908118654584,"endowment":4.465908118654584,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19559674","pmcid":null,"openalex_id":"https://openalex.org/W2123572832","authors":[],"funders":[],"total_grants":0,"fwci":2.664,"citation_percentile":0.89025725,"influential_citations":0,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":7},{"year":2014,"count":7},{"year":2015,"count":3},{"year":2016,"count":5},{"year":2017,"count":4},{"year":2018,"count":4},{"year":2019,"count":7},{"year":2020,"count":7},{"year":2021,"count":12},{"year":2022,"count":3},{"year":2023,"count":3},{"year":2024,"count":1},{"year":2025,"count":3},{"year":2026,"count":2}],"oa_status":"closed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0006291X09012698?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0006291X09012698?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bbrc.2009.06.113","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19559674","host_type":"repository"}],"fields_of_study":["Sirtuins and Resveratrol in Medicine","Calcium signaling and nucleotide metabolism","Autophagy in Disease and Therapy","Antineoplastic Agents","Benzothiazoles","Cell Line, Tumor","Enzyme Inhibitors","Humans","Inhibitory Concentration 50","Sirtuin 2","Sirtuins"],"mesh_terms":["Antineoplastic Agents","Enzyme Inhibitors","Humans","Inhibitory Concentration 50","Sirtuins","Cell Line, Tumor","Benzothiazoles","Sirtuin 2"],"keywords":["SIRT2","Sirtuin","Acetylation","Cytotoxicity","Histone","SIRT3","Chemistry","Small molecule","Biochemistry","Cell biology","In vitro","Biology","Cancer research","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T13:24:23.898075Z","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":[]}