{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:04:36Z","timestamp":1784300676761,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,12,26]],"date-time":"2017-12-26T00:00:00Z","timestamp":1514246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2017,12,26]],"date-time":"2017-12-26T00:00:00Z","timestamp":1514246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004375","name":"Tel Aviv University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004375","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001698","name":"Israel Cancer Research Fund","doi-asserted-by":"publisher","award":["0601564411"],"award-info":[{"award-number":["0601564411"]}],"id":[{"id":"10.13039\/100001698","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>The HDAC inhibitory activity of valproic acid (VPA) has led to on\u2010going evaluation of it as an anticancer agent. The histone deacetylase (HDAC) inhibitor AN446, a prodrug of VPA, releases the acid upon metabolic degradation. AN446 is &gt;60\u2010fold more potent than VPA in killing cancer cells in vitro. Herein, we compare the activities of AN446, as an anticancer agent, to those of representative types from each of the four major classes of HDAC inhibitors (HDACIs): vorinostat, romidepsin, entinostat, and VPA. AN446 exhibited the greatest selectivity and HDAC inhibitory activity against cancer cells. In glioblastoma cells only AN446, and in MDA\u2010MB\u2010231 cells only AN446 and VPA interacted in synergy with doxorubicin (Dox). AN446 was superior to the studied HDACIs in inducing DNA\u2010damage in cancer cells, while in normal astrocytes and cardiomyoblasts AN446 was the least toxic. AN446 was the only HDACI tested that exhibited selective HDAC inhibitory activity that was high in cancer cells and low in noncancerous cells. This discriminating inhibition correlated with the toxicity of the HDACIs, suggesting that their effects could be attributed to HDAC inhibition. In cardiomyoblasts, the HDACIs tested, except for AN446, hampered DNA repair by reducing the level of Rad 51. VPA and AN446 were the most effective HDACIs in inhibiting in vitro migration and invasion. The advantages of AN446 shown here, position it as a potentially improved HDACI for treatment of glioblastoma and triple negative breast cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcb.26512","type":"journal-article","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T08:18:35Z","timestamp":1510647515000},"page":"3417-3428","source":"Crossref","is-referenced-by-count":16,"title":["Comparison of the anticancer properties of a novel valproic acid prodrug to leading histone deacetylase inhibitors"],"prefix":"10.1002","volume":"119","author":[{"given":"Nataly","family":"Tarasenko","sequence":"first","affiliation":[{"name":"Felsenstein Medical Research Center, Sackler Faculty of Medicine Tel\u2010Aviv University, Beilinson Campus Petach\u2010Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Chekroun\u2010Setti","sequence":"additional","affiliation":[{"name":"Felsenstein Medical Research Center, Sackler Faculty of 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