{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T18:42:19Z","timestamp":1794336139135,"version":"4.9.0"},"reference-count":86,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Bruton tyrosine kinase (BTK) is an essential enzyme in the signaling pathway of the B-cell receptor (BCR) and is vital for the growth and activation of B-cells. Dysfunction of BTK has been linked to different types of B-cell cancers, autoimmune conditions, and inflammatory ailments. Therefore, focusing on BTK has become a hopeful approach in the field of therapeutics. Small-molecule inhibitors of BTK have been developed to selectively inhibit its activity and disrupt B-cell signaling pathways. These inhibitors bind to the active site of BTK and prevent its phosphorylation, leading to the inhibition of downstream signaling cascades. Regulatory authorities have granted approval to treat B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), with multiple small-molecule BTK inhibitors. This review offers a comprehensive analysis of the synthesis and clinical application of conventional small-molecule BTK inhibitors at various clinical stages, as well as presents promising prospects for the advancement of new small-molecule BTK inhibitors.<\/jats:p>","DOI":"10.3390\/molecules28248037","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T14:12:51Z","timestamp":1702303971000},"page":"8037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Comprehensive Review of Small-Molecule Inhibitors Targeting Bruton Tyrosine Kinase: Synthetic Approaches and Clinical Applications"],"prefix":"10.3390","volume":"28","author":[{"given":"Qi","family":"Zhang","sequence":"first","affiliation":[{"name":"Nanyang Central Hospital, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changming","family":"Wen","sequence":"additional","affiliation":[{"name":"Nanyang Central Hospital, Nanyang 473000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Rogel Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yatao","family":"Wang","sequence":"additional","affiliation":[{"name":"First People\u2019s Hospital of Shangqiu, Shangqiu 476100, China"},{"name":"Department of Orthopedics, China-Japan Union Hospital, Jilin University, Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12943-018-0779-z","article-title":"Role of Bruton\u2019s tyrosine kinase in B cells and malignancies","volume":"17","author":"Dammeijer","year":"2018","journal-title":"Mol. 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