{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:13:43Z","timestamp":1785816823371,"version":"3.56.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,10,3]],"date-time":"2013-10-03T00:00:00Z","timestamp":1380758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"HemaQuest Pharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>2,2\u2010dimethylbutyrate (HQK\u20101001), an orally\u2010bioavailable promoter\u2010targeted fetal globin gene\u2010inducing agent, was evaluated in an open\u2010label, randomized dose\u2010escalation study in 52 subjects with hemoglobin SS or S\/\u03b2<jats:sup>0<\/jats:sup> thalassemia. HQK\u20101001 was administered daily for 26 weeks at 30 mg\/kg (n = 15), 40 mg\/kg (n = 18) and 50 mg\/kg (n = 19), either alone (n = 21) or with hydroxyurea (n = 31). The most common drug\u2010related adverse events were usually mild or moderate and reversible. Gastritis was graded as severe in three subjects at 40 mg\/kg and was considered the dose\u2010limiting toxicity. Subsequently all subjects were switched to the maximum tolerated dose of 30 mg\/kg. Due to early discontinuations for blood transfusions, adverse events or non\u2010compliance, only 25 subjects (48%) completed the study. Drug plasma concentrations were sustained above targeted levels at 30 mg\/kg. Increases in fetal hemoglobin (Hb F) were observed in 42 subjects (80%), and 12 (23%) had increases \u22654%. The mean increase in Hb F was 2% [95% confidence interval (CI), 0.8\u20133.2%] in 21 subjects receiving HQK\u20101001 alone and 2.7% (95% CI, 1.7\u20133.8%) in 31 subjects receiving HQK\u20101001 plus hydroxyurea. Total hemoglobin increased by a mean of 0.65 g\/dL (95% CI, 0.5\u20131.0 g\/dL), and 13 subjects (25%) had increases \u22651 g\/dL. Future studies are warranted to evaluate the therapeutic potential of HQK\u20101001 in sickle cell disease. Am. J. Heamtol. 88:E255\u2013E260, 2013. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.23533","type":"journal-article","created":{"date-parts":[[2013,7,5]],"date-time":"2013-07-05T08:11:12Z","timestamp":1373011872000},"source":"Crossref","is-referenced-by-count":31,"title":["A dose\u2010escalation phase IIa study of 2,2\u2010dimethylbutyrate (HQK\u20101001), an oral fetal globin inducer, in sickle cell disease"],"prefix":"10.1002","volume":"88","author":[{"given":"Abdullah","family":"Kutlar","sequence":"first","affiliation":[{"name":"Adult Sickle Cell Center, Georgia Regents University Medical Center Augusta, GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin E.","family":"Reid","sequence":"additional","affiliation":[{"name":"Sickle Cell Unit, University of West Indies Medical Center at Mona Mona, Kingston Jamaica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adlette","family":"Inati","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rafik Hariri University Hospital Bir Hassan, Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali T.","family":"Taher","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, American University of Beirut Medical Center Riad El Solh, Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel R.","family":"Abboud","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, American University of Beirut Medical Center Hamra, Beirut  Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"El\u2010Beshlawy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cairo University Pediatric Hospital Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George R.","family":"Buchanan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University of Texas Southwestern Medical Center Dallas,TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedy","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tufts University Medical Center Boston, MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth I.","family":"Ataga","sequence":"additional","affiliation":[{"name":"Comprehensive Sickle Cell Program, University of North Carolina Chapel Hill, NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan P.","family":"Perrine","sequence":"additional","affiliation":[{"name":"Hemoglobinopathy Thalassemia Research Unit, Boston University Cancer Center Boston, MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Ghalie","sequence":"additional","affiliation":[{"name":"HemaQuest Pharmaceuticals, 11995 El Camino Real San Diego CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505183322001"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21699"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60355-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-364190"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.15.4842"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V62.2.370.370"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.7.2379"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1738"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V114.22.2568.2568"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-204990"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199301143280202"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506153322404"},{"key":"e_1_2_6_14_1","first-page":"790","article-title":"Sustained induction of fetal hemoglobin by pulse butyrate therapy in sickle cell disease","volume":"93","author":"Atweh GF","year":"1999","journal-title":"Blood"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08395.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.1.339.339"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21104"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.2.891"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20575"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.1.9.9"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199301143280201"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.10.2555.2555"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V110.11.79.79"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.09.044"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-392340"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0353"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-010934"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.10.3259"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2005.06.007"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2009.01234.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010379810"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23306"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12304"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.1.43.bloodjournal85143"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-01-024703"},{"key":"e_1_2_6_36_1","first-page":"355","article-title":"Choleretic effect of structural analogs of valproic acid in the rat","volume":"39","author":"Watkins JB","year":"1983","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1997.tb03685.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406093302303"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.562"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035477"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.050336"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.23533","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.23533","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.23533","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajh.23533","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.23533","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T14:55:48Z","timestamp":1692543348000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.23533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,3]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1002\/ajh.23533"],"URL":"https:\/\/doi.org\/10.1002\/ajh.23533","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,3]]}}}