{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:30:25Z","timestamp":1780403425223,"version":"3.54.1"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010888","name":"Wuhan Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["2016060101010049 to Jing Liu"],"award-info":[{"award-number":["2016060101010049 to Jing Liu"]}],"id":[{"id":"10.13039\/501100010888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010888","name":"Wuhan Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["2016060101010049"],"award-info":[{"award-number":["2016060101010049"]}],"id":[{"id":"10.13039\/501100010888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672946"],"award-info":[{"award-number":["81672946"]}],"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":["81471588"],"award-info":[{"award-number":["81471588"]}],"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":["81472735"],"award-info":[{"award-number":["81472735"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Myeloid differentiation factor 88 (MyD88) plays a key role in tumor proliferation and metastasis. Targeting MyD88 is a potent strategy in tumor therapy. TJ\u2010M2010\u20105 is a small molecule derivative of aminothiazole and could inhibit dimer formation of MyD88. To explore the potential of TJ\u2010M2010\u20105 in tumor therapy, we determined its antitumor effect and correlate mechanisms of TJ\u2010M2010\u20105 in hepatocellular carcinoma (HCC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The antitumor effect of intratumoral injection of TJ\u2010M2010\u20105 to H22 tumor\u2010bearing BALB\/c mice was observed. Tumor growth was monitored. The expression of MyD88 and Ki\u201067 were detected by immunofluorescence. <jats:italic>In vitro<\/jats:italic>, the impacts of TJ\u2010M2010\u20105 on proliferation, cell cycle, necrosis, and apoptosis of H22 cells were evaluated. The direct and indirect effects of TJ\u2010M2010\u20105 on macrophages were evaluated using flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TJ\u2010M2010\u20105 induced both G<jats:sub>0<\/jats:sub>\/G<jats:sub>1<\/jats:sub> and G<jats:sub>1<\/jats:sub>\/S phase arrests in HCC cells. Mechanically, downstream activation of MyD88 was suppressed by TJ\u2010M2010\u20105 through the extracellular regulated protein kinase\u20101\/2\/p90 ribosomal S6 kinase\/glycogen synthase kinase\u20103\u03b2 signaling pathway. In turn, cyclin\u2010dependent kinase (CDK)6\/cyclin D1 and CDK2\/cyclin E complexes were downregulated. More importantly, TJ\u2010M2010\u20105 significantly inhibited tumor growth in mice. Additionally, the portion of antitumor M1 macrophages (F4\/80<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup>) in the tumor microenvironment were increased after TJ\u2010M2010\u20105 treatment. Together, these data indicate that TJ\u2010M2010\u20105 is a promising therapeutic drug for HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results indicate that MyD88 is a feasible target for antitumor treatment and TJ\u2010M2010\u20105 is a qualified candidate for HCC therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13359","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T02:23:22Z","timestamp":1557455002000},"page":"1182-1194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Implication of myeloid differentiation factor 88 inhibitor TJ\u2010M2010\u20105 for therapeutic intervention of hepatocellular carcinoma"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3467-9392","authenticated-orcid":false,"given":"Jing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology 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