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In 2004, the Safo group reported that 5\u2010HMF has potent antisickling activity by targeting and ameliorating the primary pathophysiology of hypoxia\u2010induced sickling of erythrocytes (red blood cells [RBC]). Following the encouraging outcome of the preclinical and phase I\/II clinical studies of 5\u2010HMF for the treatment of sickle cell disease (SCD), there have been multiple studies suggesting 5\u2010HMF has several other biological or pharmacologic activities, including anti\u2010allergic, antioxidant, anti\u2010hypoxic, anti\u2010ischemic, cognitive improvement, anti\u2010tyrosinase, anti\u2010proliferation, cytoprotective, and anti\u2010inflammatory activities. The wide range of its effects makes 5\u2010HMF a potential candidate for treating a variety of diseases including cognitive disorders, gout, allergic disorders, anemia, hypoxia, cancers, ischemia, hemorrhagic shock, liver fibrosis, and oxidative injury. Several of these therapeutic claims are currently under investigation and, while promising, vary in terms of the strength of their evidence. This review presents the research regarding the therapeutic potential of 5\u2010HMF in addition to its sources, physicochemical properties, safety, absorption, distribution, metabolism, and excretion (ADME) profiles.<\/jats:p>","DOI":"10.1002\/med.22062","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T09:29:05Z","timestamp":1717666145000},"page":"2707-2729","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The antisickling agent, 5\u2010hydroxymethyl\u20102\u2010furfural: Other potential pharmacological applications"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4848-2673","authenticated-orcid":false,"given":"Piyusha P.","family":"Pagare","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"McGinn","sequence":"additional","affiliation":[{"name":"The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohini S.","family":"Ghatge","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Virginia Commonwealth University Richmond Virginia USA"},{"name":"The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vibha","family":"Shekhar","sequence":"additional","affiliation":[{"name":"The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana T.","family":"Alhashimi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Virginia Commonwealth University Richmond Virginia USA"},{"name":"The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0004-2054","authenticated-orcid":false,"given":"B.","family":"Daniel Pierce","sequence":"additional","affiliation":[{"name":"Division of Hematology The Children's Hospital of Philadelphia  Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-4291","authenticated-orcid":false,"given":"Osheiza","family":"Abdulmalik","sequence":"additional","affiliation":[{"name":"Department of Biology University of Richmond Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Virginia Commonwealth University Richmond Virginia USA"},{"name":"The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9536-1743","authenticated-orcid":false,"given":"Martin K.","family":"Safo","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Virginia Commonwealth University Richmond Virginia USA"},{"name":"The Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"PubChem. 5\u2010Hydroxymethylfurfural. 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