{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:50:11Z","timestamp":1761061811175,"version":"3.40.5"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Voxelotor is an allosteric haemoglobin (Hb) modulator that binds covalently and reversibly to Hb alpha chain to facilitate improved Hb\u2010O<jats:sub>2<\/jats:sub> affinity and arterial oxygen. It, therefore, reduces the susceptibility of erythrocytes carrying Haemoglobin S to sickle. In this study, we have used GBT1118, an analog of voxelotor, to treat male Townes sickle cell disease (SCD) mice to investigate whether the Hb modulator could attenuate the intestinal pathophysiologic changes associated with SCD. Compared with mice fed with control chow, GBT1118\u2010treated mice showed improvement in the intestinal pathophysiology. These mice exhibited improved small intestinal barrier functions, reduced intestinal microbial density, reduced enterocyte injury, lower serum lipopolysaccharides and smaller spleens. These improvements were observed after only 3\u2009weeks of GBT1118 treatment. Benefits were also observed after experimentally\u2010induced vaso\u2010occlusive crisis (VOC). Recovery from the VOC\u2010induced changes was faster in mice that were treated with GBT1118. The improved small intestinal barrier function was associated with higher expression of genes encoding enterocyte E\u2010cadherin, JAM\u2010A, ZO\u20101, MUC\u20102 and occludin while the lower intestinal microbial density associated with higher expression of genes encoding the antimicrobial peptides defensin\u2010\u03b1 1 and defensin\u2010\u03b1 4. Our findings provide the evidence to support the beneficial effects of GBT1118 in SCD\u2010related intestinal pathophysiology.<\/jats:p>","DOI":"10.1111\/bjh.18813","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T11:19:17Z","timestamp":1681384757000},"page":"184-194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of <scp>GBT1118<\/scp>, a voxelotor analog, on intestinal pathophysiology in sickle cell disease"],"prefix":"10.1111","volume":"202","author":[{"given":"Elio","family":"Haroun","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine State University of New York Upstate Medical University  Syracuse New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dibyendu","family":"Dutta","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine State 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