{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:10:25Z","timestamp":1784725825651,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,2,9]],"date-time":"2007-02-09T00:00:00Z","timestamp":1170979200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> The developmental toxicity potential of vorinostat (suberoylanilide hydroxamic acid [SAHA], ZOLINZA\u2122), a potent inhibitor of histone deacetylase (HDAC), was assessed in Sprague\u2010Dawley rats and Dutch Belted rabbits. HDAC inhibitors have been shown to mediate the regulation of gene expression, induce cell growth, cell differentiation, and apoptosis of tumor cells. Range\u2010finding studies established oral dose levels of 5, 15, or 50\u2009mg\/kg\/day and 20, 50, or 150\u2009mg\/kg\/day in rats and rabbits, respectively. <jats:bold>METHODS:<\/jats:bold> Animals were dosed on Gestation Days 6\u201320 or 7\u201320, respectively, with litter\/fetal parameters evaluated on GD 21 and 28, respectively. Separate studies evaluated toxicokinetic parameters at the mid\u2010 and high\u2010dose levels. <jats:bold>RESULTS:<\/jats:bold> There was no maternal toxicity observed at the highest dose levels; however, hematology and serum biochemistry changes were characterized in the range\u2010finding studies. Vorinostat did not induce morphological malformations in either rat or rabbit fetuses. In rats, drug\u2010related developmental toxicity was observed only in the high\u2010dose group and consisted of markedly decreased fetal weight and increases in fetuses with a limited number of skeletal variations. In rabbits, drug\u2010related developmental toxicity was also observed only in the high\u2010dose group and consisted of slightly decreased fetal weight and increases in fetuses with a short 13th rib and incomplete ossification of metacarpals. Maternal exposures to vorinostat based on AUC and Cmax values were comparable at the high\u2010dose levels of both species. Rabbits tolerated higher dosages probably due to more extensive metabolism. Maternal concentrations of vorinostat were \u223c1,000\u2013fold above the known in vitro HDAC inhibitory concentration. <jats:bold>CONCLUSIONS:<\/jats:bold> Review of previous work with valproic acid, another HDAC inhibitor, suggest that the developmental toxicity profiles of these 2 compounds are not the result of HDAC inhibition but involve other mechanisms. <jats:italic>Birth Defects Res (Part B)<\/jats:italic> 80:57\u201368, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20104","type":"journal-article","created":{"date-parts":[[2007,2,9]],"date-time":"2007-02-09T22:17:35Z","timestamp":1171059455000},"page":"57-68","source":"Crossref","is-referenced-by-count":31,"title":["Assessment of developmental toxicity of vorinostat, a histone deacetylase inhibitor, in Sprague\u2010Dawley rats and Dutch Belted rabbits"],"prefix":"10.1002","volume":"80","author":[{"given":"L. David","family":"Wise","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie J.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet S.","family":"Kerr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,2,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(88)90112-1"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2133"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01166"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20021321"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx0502241"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3425fje"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420380405"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-04-0070"},{"key":"e_1_2_6_10_1","first-page":"3578","article-title":"Phase I clinical trial of histone deacetylase inhibitor: Suberoylanilide hydroxamic acid administered intravenously","volume":"9","author":"Kelly WK","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.14.167"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.6.1176"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.11.2672"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200111000-00010"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/35106079"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(03)00084-5"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20053"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(85)90081-X"},{"key":"e_1_2_6_19_1","first-page":"1247","article-title":"Inhibition of histone deacetylase activity by trichostatin A modulates gene expression during mouse embryogenesis without apparent toxicity","volume":"61","author":"Nervi C","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-0590(83)80067-0"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408440590935639"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420340305"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101287200"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000809"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006091014092"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.8.3132-3139.2004"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420350205"}],"container-title":["Birth Defects Research Part B: Developmental and Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdrb.20104","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdrb.20104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T08:54:42Z","timestamp":1700038482000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdrb.20104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,2]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,2]]}},"alternative-id":["10.1002\/bdrb.20104"],"URL":"https:\/\/doi.org\/10.1002\/bdrb.20104","archive":["Portico"],"relation":{},"ISSN":["1542-9733","1542-9741"],"issn-type":[{"value":"1542-9733","type":"print"},{"value":"1542-9741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,2]]}}}