{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:29:42Z","timestamp":1786685382393,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp;amp; Perspec"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    CD148 is the primary receptor\u2010type protein tyrosine phosphatase (PTP) regulating platelet activation, and its inhibition has been proposed as a novel anti\u2010thrombotic strategy with potentially lower bleeding risk than current therapies. However, selective and potent inhibitors of CD148 are currently lacking. AKB\u20109778 (razuprotafib), a potent inhibitor of the closely related vascular endothelial\u2010PTP (VE\u2010PTP), has also been reported to inhibit CD148. This study investigated the effect of AKB\u20109778 on in\u00a0vitro whole\u2010blood thrombogenicity, examined the molecular basis of its interaction with the CD148 catalytic domain using molecular docking, and assessed inhibitor selectivity with an in\u00a0vitro phosphatase assay. In a total\u2010thrombus formation analysis system (T\u2010TAS), AKB\u20109778 partially inhibited thrombus formation, reducing AUC\n                    <jats:sub>10<\/jats:sub>\n                    by 28%, without significantly affecting occlusion start time or occlusion time. The inhibitor did not alter collagen\u2010stimulated CD62P platelet surface expression or PAC\u20101 binding to the activated integrin \u03b1IIb\u03b23. Molecular docking using CB\u2010Dock predicted a binding configuration in which the phenylsulfamic acid group of AKB\u20109778 is orientated towards the catalytic cysteine, with additional conformations reflecting ligand flexibility. Site\u2010directed mutagenesis of Tyr1071, Gln1283, His1206, and Asn1073 to alanine reduced the inhibitory effect in phosphatase assays, supporting interaction with these residues. Notably, the IC\n                    <jats:sub>50<\/jats:sub>\n                    of AKB\u20109778 against CD148 was approximately 300\u2010fold higher than previously reported values, consistent with the wide variability across studies. Despite this reduced potency, these findings support the concept of CD148 inhibition as a potential anti\u2010thrombotic strategy and suggest that AKB\u20109778 may serve as a useful prototype for developing more selective and efficacious CD148 inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70301","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T03:56:07Z","timestamp":1785556567000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting\n                    <scp>CD148<\/scp>\n                    for Antithrombotic Therapy: Functional and Molecular Evaluation of\n                    <scp>AKB<\/scp>\n                    \u20109778"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4404-2021","authenticated-orcid":false,"given":"Lina","family":"El Badaoui","sequence":"first","affiliation":[{"name":"School of Life Sciences University of Westminster  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4274-4070","authenticated-orcid":false,"given":"Stipo","family":"Jurcevic","sequence":"additional","affiliation":[{"name":"School of Life Sciences University of Westminster  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0947-9957","authenticated-orcid":false,"given":"Yotis A.","family":"Senis","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Nutrition Research, INSERM 1263, INRAE 1260, Faculty of Medicine Aix\u2010Marseille University  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7738-8419","authenticated-orcid":false,"given":"Alastair J.","family":"Barr","sequence":"additional","affiliation":[{"name":"School of Life Sciences University of Westminster  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102008\u201008\u2010174318"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201002\u2010768077"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23030569"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12495"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201007\u2010859496"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102012\u201004\u2010424044"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cnr2.1566"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.10.241"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2014.80"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.03.004"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.07.001"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25020820"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74527"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.09.023"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2016.04.025"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.151527"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.14.12"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.121292"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt164"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100039\u20101693411"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010019\u20100228\u20106"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.3791\/65410"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2013.05.026"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.11.038"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70233"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201010\u2010784074"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2024.123157"}],"container-title":["Pharmacology Research &amp; 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