{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:43:47Z","timestamp":1785408227034,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,15]]},"group-title":"Biochemistry","reference-count":29,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01HL153253"],"award-info":[{"award-number":["R01HL153253"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Phase 1 Technology Commercialization Award"],"award-info":[{"award-number":["Phase 1 Technology Commercialization Award"]}],"id":[{"id":"https:\/\/ror.org\/00hasdx88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  It is challenging to develop anti-thrombotic therapeutics to treat or prevent pathological thrombus formation without increasing the risk of bleeding. Currently available anti-coagulant drugs render blood thinner irrespective of whether an inflammatory pro-thrombotic condition exists or whether clotting needs to occur because of traumatic vessel rupture. It is desirable to develop a drug that is active only under the oxidizing conditions present during inflammation. The blood protein von Willebrand factor (VWF) plays a key role in initiating blood clotting and it has been the target of anti-thrombotic therapies. It has been shown that oxidizing agents released during inflammation activate VWF by converting methionine residues within its domains to methionine sulfoxide. A previous study by us developed a method to computationally screen for drugs that inhibit VWF more strongly in the presence of oxidizing conditions. The computations suggested in particular a drug, lumacaftor, that could inhibit VWF function selectively in the presence of oxidized methionine residues. Here, we developed an enzyme-linked immunosorbent assay to test the effect of drugs on the ability of VWF to bind to the platelet surface receptor glycoprotein Ib\n                  <jats:italic>\u03b1<\/jats:italic>\n                  comparing oxidizing and non-oxidizing conditions. The results indicate that lumacaftor may indeed have the desired properties of inhibiting VWF selectively when oxidized. Because of its simplicity, the assay provides a high-throughput method to efficiently screen multiple drugs against VWF in both its oxidized and unoxidized state.\n                <\/jats:p>","DOI":"10.1101\/2025.08.13.670163","type":"posted-content","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T02:00:16Z","timestamp":1755309616000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting von Willebrand factor selectively under inflammatory conditions"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5445-9587","authenticated-orcid":false,"given":"Gianluca","family":"Interlandi","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria S.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Bloodworks Research Institute, Seattle, WA 98102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6418-8629","authenticated-orcid":false,"given":"Alexander","family":"St. John","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie","family":"Le","sequence":"additional","affiliation":[{"name":"Bloodworks Research Institute, Seattle, WA 98102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmei","family":"Chen","sequence":"additional","affiliation":[{"name":"Bloodworks Research Institute, Seattle, WA 98102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Bloodworks Research Institute, Seattle, WA 98102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Fu","sequence":"additional","affiliation":[{"name":"Bloodworks Research Institute, Seattle, WA 98102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026032910404449000_2025.08.13.670163v2.1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000326895.58992.27"},{"key":"2026032910404449000_2025.08.13.670163v2.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1505533"},{"issue":"7","key":"2026032910404449000_2025.08.13.670163v2.3","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1111\/jth.13716","article-title":"Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura","volume":"15","year":"2017","journal-title":"J. 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