{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:19:00Z","timestamp":1789676340869,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T00:00:00Z","timestamp":1613779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20202009"],"award-info":[{"award-number":["BK20202009"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673443"],"award-info":[{"award-number":["81673443"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973361"],"award-info":[{"award-number":["81973361"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The protein V\u2010domain immunoglobulin suppressor of T\u2010cell activation (VISTA) is a novel immune\u2010checkpoint molecule that belongs to the B7 family and regulates a broad spectrum of immune responses. So far, low MW compounds targeting VISTA for the treatment of autoimmune diseases or inflammation, have not been identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We developed a homology modelling for VISTA 3D structure and subsequent virtual screening for low MW ligands binding to VISTA. Visualization of the binding postures of docked ligands with protein VISTA indicated that compound M351\u20100056 targeted VISTA. The biological activities of compound M351\u20100056 targeting VISTA were investigated in vitro using monocytes and T cells and in vivo, using mice with imiquimod\u2010induced dermatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The <jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub> value of M351\u20100056 for human VISTA\u2010extracellular domain was 12.60 \u00b1 3.84 \u03bcM as assessed by microscale thermophoresis. M351\u20100056 decreased cytokine secretion from PBMCs or human CD4<jats:sup>+<\/jats:sup> T cells, suppressed proliferation of PBMCs and enhanced expression of Foxp3<jats:sup>+<\/jats:sup> T cells. These effects of M351\u20100056 modulating VISTA involved the JAK2\u2013STAT2 pathway. Daily administration of M351\u20100056 ameliorated imiquimod\u2010induced psoriasis\u2010like dermatitis. Expression of mRNA and protein of inflammatory cytokines in psoriatic lesions was decreased after M351\u20100056 treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The compound M351\u20100056 showed high affinity for VISTA and may modulate its immune function in vitro and in vivo. Our finding provides a lead compound for therapeutically enhancing VISTA\u2010mediated pathways to benefit the treatment of autoimmune diseases or inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15357","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T00:38:28Z","timestamp":1610757508000},"page":"1445-1458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["M351\u20100056 is a novel low MW compound modulating the actions of the immune\u2010checkpoint protein VISTA"],"prefix":"10.1111","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4144-8923","authenticated-orcid":false,"given":"Xinlei","family":"Hu","sequence":"first","affiliation":[{"name":"Jiangsu Key Lab of Drug Screening China Pharmaceutical University  Nanjing 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