{"doi":"10.1021/acsptsci.4c00358","title":"A Novel Liver Cancer-Selective Histone Deacetylase Inhibitor Is Effective against Hepatocellular Carcinoma and Induces Durable Responses with Immunotherapy","abstract":"High Resolution Image Download MS PowerPoint Slide Hepatocellular carcinoma (HCC) progression is facilitated by gene-silencing chromatin histone hypoacetylation due to histone deacetylase (HDAC) activation. However, inhibiting HDACs─an effective treatment for lymphomas─has shown limited success in solid tumors. We report the discovery of a class of HDAC inhibitors (HDACi) that demonstrates exquisite selective cytotoxicity against human HCC cells. The lead compound STR-V-53 ( 3 ) showed a favorable safety profile in mice and robustly suppressed tumor growth in orthotopic xenograft models of HCC. When combined with the anti-HCC drug sorafenib, STR-V-53, showed greater in vivo efficacy. Moreover, STR-V-53 combined with anti-PD1 therapy increased the CD8 + to regulatory T-cell (Treg) ratio and survival in an orthotopic HCC model in immunocompetent mice. This combination therapy resulted in durable responses in 40% of the mice. Transcriptomic analysis revealed that STR-V-53 primed HCC cells to immunotherapy through HDAC inhibition, impaired glucose-regulated transcription, impaired DNA synthesis, upregulated apoptosis, and stimulated the immune response pathway. Collectively, our data demonstrate that the novel HDACi STR-V-53 is an effective anti-HCC agent that can induce profound responses when combined with standard immunotherapy.","journal":"ACS Pharmacology & Translational Science","year":2024,"id":458318,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":384270,"name":"Subhasish Tapadar","orcid":null,"position":1,"is_corresponding":false},{"id":841623,"name":"Zhiping Ruan","orcid":"0000-0001-9467-7466","position":2,"is_corresponding":false},{"id":384271,"name":"Carrie Sun","orcid":null,"position":3,"is_corresponding":false},{"id":384272,"name":"Rebecca S. Arnold","orcid":null,"position":4,"is_corresponding":false},{"id":1092403,"name":"Alexis Johnston","orcid":"0000-0001-7598-2895","position":5,"is_corresponding":false},{"id":1268488,"name":"Jeremiah Olorunjuwon Olugbami","orcid":"0000-0002-8287-2499","position":6,"is_corresponding":false},{"id":1284204,"name":"Uche O. Arunsi","orcid":"0000-0002-5315-2695","position":7,"is_corresponding":false},{"id":383128,"name":"David A. Gaul","orcid":"0000-0002-9308-1895","position":8,"is_corresponding":false},{"id":383129,"name":"John A. Petros","orcid":"0000-0002-4472-6335","position":9,"is_corresponding":false},{"id":406736,"name":"Tatsuya Kobayashi","orcid":"0000-0003-4264-5117","position":10,"is_corresponding":false},{"id":238100,"name":"Dan G. Duda","orcid":"0000-0001-7065-8797","position":11,"is_corresponding":false},{"id":383130,"name":"Adegboyega K. Oyelere","orcid":"0000-0002-2248-9551","position":12,"is_corresponding":false},{"id":383125,"name":"Bocheng Wu","orcid":"0000-0002-7381-9506","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:03:46.117860Z","pmid":"39416967","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":[]}