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It regulates key biological processes such as development, stem cell maintenance, and oncogenesis, and its aberrant expression is implicated in various cancers. Accordingly, KDM5B is considered a promising therapeutic target in cancer drug discovery. In this study, we performed a screening to identify novel inhibitors of KDM5B. Through this screening, we identified a common core scaffold associated with KDM5B inhibitory activity, and subsequent optimization of the side\u2010chain structures led to the identification of a series of compounds with IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from several nanomolar to several micromolar. Evaluation of growth inhibitory activity using the JFCR39 human cancer cell line panel revealed that the final lead compounds, JB\u2010157 and JB\u2010161, exhibited GI\n                    <jats:sub>50<\/jats:sub>\n                    values in the low micromolar range. In a xenograft model, where the human colorectal cancer cell line HT\u201029 was implanted into NOD\/SCID mice, administration of these compounds resulted in antitumour effects, with JB\u2010161 showing particularly pronounced tumor suppression in a subset of treated animals. Furthermore, combination treatment with in\u00a0vivo CAR\u2010T cell therapy and JB\u2010161 in C57BL\/6J mice was associated with alterations in chromatin accessibility in tumor and immune cell populations. Taken together, these results suggest that JB\u2010161 is a candidate KDM5B inhibitor associated with chromatin accessibility changes and antitumour activity.\n                  <\/jats:p>","DOI":"10.1002\/cam4.72058","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T03:35:08Z","timestamp":1782099308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Novel Small\u2010Molecule Inhibitors Targeting\n                    <scp>KDM5B<\/scp>\n                    and Evaluation of Their Antitumour Effects"],"prefix":"10.1002","volume":"15","author":[{"given":"Tomoaki","family":"Hara","sequence":"first","affiliation":[{"name":"Department of Medical Data Science, Center of Medical Innovation and Translational Research Graduate School of Medicine, The University of Osaka  Suita Osaka 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