Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2c, 15-222 Bialystok, Poland.
Department of Clinical Pharmacy, Medical University of Bialystok, Mickiewicza 2c, 15-222 Bialystok, Poland.
Molecules. 2023 Mar 6;28(5):2400. doi: 10.3390/molecules28052400.
In the last few decades, there has been a growing interest in Bruton's tyrosine kinase (BTK) and the compounds that target it. BTK is a downstream mediator of the B-cell receptor (BCR) signaling pathway and affects B-cell proliferation and differentiation. Evidence demonstrating the expression of BTK on the majority of hematological cells has led to the hypothesis that BTK inhibitors (BTKIs) such as ibrutinib can be an effective treatment for leukemias and lymphomas. However, a growing body of experimental and clinical data has demonstrated the significance of BTK, not just in B-cell malignancies, but also in solid tumors, such as breast, ovarian, colorectal, and prostate cancers. In addition, enhanced BTK activity is correlated with autoimmune disease. This gave rise to the hypothesis that BTK inhibitors can be beneficial in the therapy of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), Sjögren's syndrome (SS), allergies, and asthma. In this review article, we summarize the most recent findings regarding this kinase as well as the most advanced BTK inhibitors that have been developed to date and their clinical applications mainly in cancer and chronic inflammatory disease patients.
在过去几十年中，人们对布鲁顿酪氨酸激酶（BTK）及其靶向化合物的兴趣日益浓厚。BTK 是 B 细胞受体（BCR）信号通路的下游介质，影响 B 细胞的增殖和分化。有证据表明，BTK 表达于大多数血液细胞上，这使得人们假设 BTK 抑制剂（BTKi）如伊布替尼可有效治疗白血病和淋巴瘤。然而，越来越多的实验和临床数据表明，BTK 不仅在 B 细胞恶性肿瘤中具有重要意义，而且在乳腺癌、卵巢癌、结直肠癌和前列腺癌等实体瘤中也具有重要意义。此外，BTK 活性的增强与自身免疫性疾病有关。这就提出了一个假设，即 BTK 抑制剂可能有益于类风湿关节炎（RA）、系统性红斑狼疮（SLE）、多发性硬化症（MS）、干燥综合征（SS）、过敏和哮喘的治疗。在这篇综述文章中，我们总结了关于这种激酶的最新发现，以及迄今为止开发的最先进的 BTK 抑制剂，及其在癌症和慢性炎症性疾病患者中的主要临床应用。
