{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:07:13Z","timestamp":1785528433371,"version":"3.56.0"},"reference-count":96,"publisher":"Informa UK Limited","issue":"4","content-domain":{"domain":["www.tandfonline.com"],"crossmark-restriction":true},"short-container-title":["Expert Opinion on Investigational Drugs"],"published-print":{"date-parts":[[2025,4,3]]},"DOI":"10.1080\/13543784.2025.2500289","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T10:27:53Z","timestamp":1746440873000},"page":"301-315","update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":1,"title":["Preclinical therapeutics for sickle cell disease: modern developments and future considerations"],"prefix":"10.1080","volume":"34","author":[{"given":"Iheanyi","family":"Okpala","sequence":"first","affiliation":[{"name":"University of Nigeria Teaching Hospital","place":["Enugu, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Nonyelu","sequence":"additional","affiliation":[{"name":"University of Nigeria Teaching Hospital","place":["Enugu, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebele","family":"Muoghalu","sequence":"additional","affiliation":[{"name":"University of Nigeria Teaching Hospital","place":["Enugu, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikechukwu","family":"Anigbogu","sequence":"additional","affiliation":[{"name":"University of Nigeria Teaching Hospital","place":["Enugu, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinenye","family":"Onodugo","sequence":"additional","affiliation":[{"name":"University of Nigeria Teaching Hospital","place":["Enugu, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udoka","family":"Ilechukwu","sequence":"additional","affiliation":[{"name":"University of Nigeria Teaching Hospital","place":["Enugu, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwaoma","family":"Fidelis-Ewa","sequence":"additional","affiliation":[{"name":"University of Nigeria Teaching Hospital","place":["Enugu, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustine","family":"Duru","sequence":"additional","affiliation":[{"name":"University of Nigeria Teaching Hospital","place":["Enugu, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Okoye","sequence":"additional","affiliation":[{"name":"University of Nigeria Teaching Hospital","place":["Enugu, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"301","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"e_1_3_5_3_1","first-page":"47","volume-title":"Synopsis of hematology","author":"Okpala I.","year":"2010","unstructured":"Okpala I. Sickle cell disease and thalassaemia. In: Okpala I Johnson C, editors. Synopsis of hematology. Charleston [SC (USA)]: CreateSpace Publishers; 2010. p. 47\u201370."},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03691.x"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0009922814533418"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/17.2.113"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12878-018-0098-z"},{"key":"e_1_3_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00540-9"},{"key":"e_1_3_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470988398.ch1"},{"key":"e_1_3_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470988398.ch3"},{"key":"e_1_3_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/180326a0"},{"key":"e_1_3_5_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89741"},{"key":"e_1_3_5_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10245330400001926"},{"key":"e_1_3_5_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.moh.0000190108.62414.06"},{"key":"e_1_3_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-960X(03)00037-7"},{"key":"e_1_3_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2005.08.004"},{"key":"e_1_3_5_17_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.15.8.833"},{"key":"e_1_3_5_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2015.963552"},{"key":"e_1_3_5_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/03630269809071538"},{"key":"e_1_3_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0037-1963(01)90023-X"},{"issue":"3","key":"e_1_3_5_21_1","first-page":"15","article-title":"Mechanism of action of hydroxyurea in the management of sickle cell anemia in adults","volume":"34","author":"Charache S","year":"1997","unstructured":"Charache S. Mechanism of action of hydroxyurea in the management of sickle cell anemia in adults. Semin Hematol. 1997;34(Suppl 3):15\u201321.","journal-title":"Semin Hematol"},{"key":"e_1_3_5_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198504043121403"},{"key":"e_1_3_5_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830140412"},{"key":"e_1_3_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.03.067"},{"key":"e_1_3_5_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-179331"},{"key":"e_1_3_5_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adk6129"},{"key":"e_1_3_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35404-0"},{"key":"e_1_3_5_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1101501"},{"key":"e_1_3_5_29_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0311095"},{"key":"e_1_3_5_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023012467"},{"issue":"1","key":"e_1_3_5_31_1","first-page":"25","article-title":"Safety and efficacy of etavopivat, a pyruvate kinase activator, in adults with sickle cell disease: a phase 1\/2 randomized, double-blind, placebo-controlled trial","volume":"136","author":"Townes TM","year":"2020","unstructured":"Townes TM, Westerman KA, Endicott SK, et al. Safety and efficacy of etavopivat, a pyruvate kinase activator, in adults with sickle cell disease: a phase 1\/2 randomized, double-blind, placebo-controlled trial. Blood. 2020;136(Supplement 1):25\u201326.","journal-title":"Blood"},{"issue":"2","key":"e_1_3_5_32_1","first-page":"341","article-title":"Safety and tolerability of etavopivat in patients with sickle cell disease: a phase 1 study","volume":"193","author":"Vichinsky EP","year":"2021","unstructured":"Vichinsky EP, Earley E, Johnson C, et al. Safety and tolerability of etavopivat in patients with sickle cell disease: a phase 1 study. Br J Haematol. 2021;193(2):341\u2013345.","journal-title":"Br J Haematol"},{"key":"e_1_3_5_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011477"},{"key":"e_1_3_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2005.08.002"},{"key":"e_1_3_5_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.6.1955"},{"key":"e_1_3_5_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.9.3356"},{"key":"e_1_3_5_37_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0609.2002.02775.x"},{"key":"e_1_3_5_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-034147"},{"key":"e_1_3_5_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.HS9.0000848800.77383.3d"},{"key":"e_1_3_5_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-553X.2007.00961.x"},{"key":"e_1_3_5_41_1","doi-asserted-by":"publisher","DOI":"10.4314\/gmj.v57i3.6"},{"key":"e_1_3_5_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-140530"},{"key":"e_1_3_5_43_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611770"},{"key":"e_1_3_5_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000233"},{"key":"e_1_3_5_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2022.2143260"},{"key":"e_1_3_5_46_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1657501"},{"key":"e_1_3_5_47_1","unstructured":"Pfizer Inc [USA]. Pfizer voluntarily withdraws all lots of sickle cell disease treatment OXBRYTA\u00ae (voxelotor) from worldwide markets. [cited 2024 Oct 19]. Available from: https:\/\/www.pfizer.com\/news\/press-release\/press-release-detail\/pfizer-voluntarily-withdraws-all-lots-sickle-cell-diseasetreatmentoxybryta\u00ae(voxelotor)fromworldwidemarkets"},{"key":"e_1_3_5_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.6b00491"},{"key":"e_1_3_5_49_1","volume-title":"Abstract Number S291 presented at the annual conference of the European Haematology Association","author":"Saraf S","year":"2024","unstructured":"Saraf S, Abdullahi S, Akinsete AM, et al. Preliminary results from a multicenter phase 2\/3 study of next-generation HbS polymerization inhibitor osivelotor (GBT021601) for the treatment of patients with sickle cell disease. In: Abstract Number S291 presented at the annual conference of the European Haematology Association; Madrid, Spain; 2024 Jun 13\u201316."},{"key":"e_1_3_5_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26204"},{"key":"e_1_3_5_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-023-00429-7"},{"key":"e_1_3_5_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11111843"},{"key":"e_1_3_5_53_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2029392"},{"key":"e_1_3_5_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02636-6"},{"key":"e_1_3_5_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-023-00390-5"},{"key":"e_1_3_5_56_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309676"},{"key":"e_1_3_5_57_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2117175"},{"key":"e_1_3_5_58_1","doi-asserted-by":"publisher","DOI":"10.1024\/0300-9831.78.3.139"},{"key":"e_1_3_5_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8652(199806)58:2<117::AID-AJH5>3.0.CO;2-V"},{"key":"e_1_3_5_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1715971"},{"key":"e_1_3_5_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2021.106546"},{"key":"e_1_3_5_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.931925"},{"key":"e_1_3_5_63_1","unstructured":"U.S. of America Food and Drug Administration (FDA). FDA approves new treatment for sickle cell disease. FDA News Release 2017; 2017. Available online at https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-new-treatment-sickle-cell-disease"},{"key":"e_1_3_5_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-005-1023-7"},{"key":"e_1_3_5_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2005.03.005"},{"key":"e_1_3_5_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2005.10.002"},{"key":"e_1_3_5_67_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018021444"},{"key":"e_1_3_5_68_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615948"},{"key":"e_1_3_5_69_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.112.036319"},{"key":"e_1_3_5_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2011.02751.x"},{"key":"e_1_3_5_71_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/236374"},{"key":"e_1_3_5_72_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197210192871606"},{"key":"e_1_3_5_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(91)90156-W"},{"key":"e_1_3_5_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.05.085"},{"key":"e_1_3_5_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.07.041"},{"key":"e_1_3_5_76_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1345411"},{"key":"e_1_3_5_77_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100225"},{"key":"e_1_3_5_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.05.015"},{"key":"e_1_3_5_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2015.03.014"},{"key":"e_1_3_5_80_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205028"},{"issue":"4","key":"e_1_3_5_81_1","first-page":"227","article-title":"Youth of West Cameroon are at high risk of developing IDD due to low dietary iodine and high dietary thiocyanate","volume":"8","author":"Taga I","year":"2008","unstructured":"Taga I, Oumbe VAS, Johns R, et al. Youth of West Cameroon are at high risk of developing IDD due to low dietary iodine and high dietary thiocyanate. Afr Health Sci. 2008;8(4):227\u2013233.","journal-title":"Afr Health Sci"},{"key":"e_1_3_5_82_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505183322001"},{"key":"e_1_3_5_83_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2015.1088827"},{"key":"e_1_3_5_84_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00205.2020"},{"key":"e_1_3_5_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.02.073"},{"key":"e_1_3_5_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420505"},{"key":"e_1_3_5_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-004-1282-9"},{"key":"e_1_3_5_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2021.102564"},{"key":"e_1_3_5_89_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2022-325106"},{"key":"e_1_3_5_90_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-184806"},{"key":"e_1_3_5_91_1","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000002146"},{"key":"e_1_3_5_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(23)00118-7"},{"key":"e_1_3_5_93_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17312"},{"key":"e_1_3_5_94_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000035237"},{"key":"e_1_3_5_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2022.03.008"},{"key":"e_1_3_5_96_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003776"},{"key":"e_1_3_5_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.03.005"},{"key":"e_1_3_5_98_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-120122-081037"}],"container-title":["Expert Opinion on Investigational Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.tandfonline.com\/doi\/pdf\/10.1080\/13543784.2025.2500289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T12:46:41Z","timestamp":1756471601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/13543784.2025.2500289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":96,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,3]]}},"alternative-id":["10.1080\/13543784.2025.2500289"],"URL":"https:\/\/doi.org\/10.1080\/13543784.2025.2500289","relation":{},"ISSN":["1354-3784","1744-7658"],"issn-type":[{"value":"1354-3784","type":"print"},{"value":"1744-7658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]},"assertion":[{"value":"The publishing and review policy for this title is described in its Aims & Scope.","order":1,"name":"peerreview_statement","label":"Peer Review Statement"},{"value":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=ieid20","URL":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=ieid20","order":2,"name":"aims_and_scope_url","label":"Aim & Scope"},{"value":"2024-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}