{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:45Z","timestamp":1787027745475,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R43CA224642"],"award-info":[{"award-number":["1R43CA224642"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Dysfunctions in epigenetic regulation play critical roles in tumor development and progression. Histone deacetylases (HDACs) and histone acetyl transferase (HAT) are functionally opposing epigenetic regulators, which control the expression status of tumor suppressor genes. Upregulation of HDAC activities, which results in silencing of tumor suppressor genes and uncontrolled proliferation, predominates in malignant tumors. Inhibition of the deacetylase activity of HDACs is a clinically validated cancer therapy strategy. However, current HDAC inhibitors (HDACi) have elicited limited therapeutic benefit against solid tumors. Here, we disclosed a class of HDACi that are selective for sub-class I HDACs and preferentially accumulate within the normal liver tissue and orthotopically implanted liver tumors. We observed that these compounds possess exquisite on-target effects evidenced by their induction of dose-dependent histone H4 hyperacetylation without perturbation of tubulin acetylation status and G0\/G1 cell cycle arrest. Representative compounds 2 and 3a are relatively non-toxic to mice and robustly suppressed tumor growths in an orthotopic model of HCC as standalone agents. Collectively, our results suggest that these compounds may have therapeutic advantage against HCC relative to the current systemic HDACi. This prospect merits further comprehensive preclinical investigations.<\/jats:p>","DOI":"10.3390\/cancers12113095","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T08:59:28Z","timestamp":1603443568000},"page":"3095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Liver-Targeting Class I Selective Histone Deacetylase Inhibitors Potently Suppress Hepatocellular Tumor Growth as Standalone Agents"],"prefix":"10.3390","volume":"12","author":[{"given":"Subhasish","family":"Tapadar","sequence":"first","affiliation":[{"name":"School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA"},{"name":"Sophia Bioscience, Inc. 311 Ferst Drive NW, Ste. L1325A, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaghayegh","family":"Fathi","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7381-9506","authenticated-orcid":false,"given":"Bocheng","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie Q.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5697-6422","authenticated-orcid":false,"given":"Idris","family":"Raji","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel G.","family":"Moore","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca S.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9308-1895","authenticated-orcid":false,"given":"David A.","family":"Gaul","sequence":"additional","affiliation":[{"name":"Sophia Bioscience, Inc. 311 Ferst Drive NW, Ste. L1325A, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Petros","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adegboyega K.","family":"Oyelere","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA"},{"name":"Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2018). Global Cancer Facts & Figures, American Cancer Society. 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