{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T23:37:29Z","timestamp":1786232249154,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2019-I2M-5-044"],"award-info":[{"award-number":["2019-I2M-5-044"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473791"],"award-info":[{"award-number":["82473791"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018541","name":"Science Fund for Distinguished Young Scholars of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20250102"],"award-info":[{"award-number":["BK20250102"]}],"id":[{"id":"10.13039\/501100018541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Activation of signal transducer and activator of transcription 3 (STAT3) is implicated in tumor progression and correlates with poor prognosis and reduced survival. In colorectal cancer (CRC), STAT3 activation serves as a key indicator of unfavorable outcomes. However, the scarcity of clinically available STAT3 inhibitors hinders the development of personalized treatment strategies targeting STAT3. Therefore, we aimed to develop a novel STAT3 inhibitor based on the molecular structure of STAT3 and our previously reported STAT3 inhibitor LY17 to inhibit the progression of CRC. The binding of the novel STAT3 inhibitor DB-2B to STAT3 was confirmed by computational docking, surface plasmon resonance, isothermal titration calorimetry, and cellular thermal shift assays. Western blotting and immunofluorescent staining demonstrated that DB-2B specifically inhibited STAT3 activation and nuclear translocation. In vitro studies revealed that DB-2B significantly suppressed proliferation, induced apoptosis, arrested cell cycle progression, and attenuated stemness by inhibiting STAT3 activation and its downstream signaling pathways. In vivo, DB-2B exhibited favorable oral bioavailability and safety, while significantly inhibiting the progression of CRC. Collectively, this study presents DB-2B as a promising small-molecule STAT3 inhibitor for the targeted treatment of CRC.<\/jats:p>","DOI":"10.3390\/biom16050752","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:14:52Z","timestamp":1779452092000},"page":"752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["DB-2B, a Novel and Selective STAT3 Inhibitor Inhibits Colorectal Cancer Progression In Vitro and In Vivo"],"prefix":"10.3390","volume":"16","author":[{"given":"Yuting","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China"},{"name":"Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042) & Zhejiang University School of Medicine, Hangzhou 310058, China"},{"name":"Department of Pathology, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianyang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixia","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042) & Zhejiang University School of Medicine, Hangzhou 310058, China"},{"name":"Department of Pathology, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-2925","authenticated-orcid":false,"given":"Zhiyong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China"},{"name":"Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042) & Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maode","family":"Lai","sequence":"additional","affiliation":[{"name":"Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042) & Zhejiang University School of Medicine, Hangzhou 310058, China"},{"name":"Department of Pathology, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1016\/j.cell.2022.09.023","article-title":"The JAK-STAT pathway at 30: Much learned, much more to do","volume":"185","author":"Philips","year":"2022","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrc3818","article-title":"Revisiting STAT3 signalling in cancer: New and unexpected biological functions","volume":"14","author":"Yu","year":"2014","journal-title":"Nat. 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