{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:32:37Z","timestamp":1787877157589,"version":"build-2784847793"},"reference-count":16,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000014","name":"Canadian Blood Services","doi-asserted-by":"publisher","award":["IRGP2024\u2010Branch"],"award-info":[{"award-number":["IRGP2024\u2010Branch"]}],"id":[{"id":"10.13039\/501100000014","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The characteristic feature of immune cytopenias involves the process of extravascular phagocytosis, wherein macrophages in the spleen and\/or liver engage in the destruction of blood cells that have been opsonized by auto\u2010 or alloantibodies. Therefore, new treatments that prevent phagocytosis will be advantageous, especially for short\u2010term usage along with alternative options.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design and Methods<\/jats:title><jats:p>KB\u2010208, a small molecule drug, previously shown to be efficacious for the in vitro inhibition of phagocytosis was synthesized. A passive antibody mouse model of immune thrombocytopenia (ITP) was used. Three different mouse strains (BALB\/c, C57BL\/6, CD1) were used to determine the efficacy of KB\u2010208 compared with IVIG to ameliorate the ITP. Toxicity was investigated after 60\u2010day chronic administration of KB\u2010208 by a biochemistry panel, gross necroscopy and histopathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>KB\u2010208 showed similar efficacy to ameliorate the thrombocytopenia compared with IVIG in all three mouse strains. This small molecule drug was effective at 1\u2009mg\/kg in ameliorating ITP, in comparison with IVIG at 1000\u20132500\u2009mg\/kg. KB\u2010208 did not affect other blood parameters or elevate serum biochemistry markers of toxicity nor were any abnormal histopathological findings found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>KB\u2010208 is similar to IVIG for the amelioration of ITP in multiple mouse strains. Chronic administration of KB\u2010208 for 60\u2009days did not demonstrate in vivo toxicity. These findings indicate that KB\u2010208 is efficacious, without significant in vivo toxicities in mice, and is a potential small molecule candidate for further evaluation to be used in the treatment of ITP and possibly all immune cytopenias where phagocytosis is responsible for the pathophysiology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.18060","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T06:29:33Z","timestamp":1731047373000},"page":"2233-2240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A novel small molecule phagocytosis inhibitor, <scp>KB<\/scp>\u2010208, ameliorates <scp>ITP<\/scp> in mouse models with similar efficacy as <scp>IVIG<\/scp>"],"prefix":"10.1111","volume":"64","author":[{"given":"Melika","family":"Loriamini","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario Canada"},{"name":"Centre for Innovation Canadian Blood Services  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa M.","family":"Lewis\u2010Bakker","sequence":"additional","affiliation":[{"name":"Krembil Research Institute University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Binnington","sequence":"additional","affiliation":[{"name":"Centre for Innovation Canadian Blood Services  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7071-4637","authenticated-orcid":false,"given":"Lakshmi P.","family":"Kotra","sequence":"additional","affiliation":[{"name":"Krembil Research Institute University Health Network  Toronto Ontario Canada"},{"name":"Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario 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