Swati Paliwal, Sandhya Bawa, Nishtha Shalmali, Rajiv K. Tonk
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Therefore, drugs targeting B cells have now become a hot topic in the treatment of RA which is quite evident from the recent trends seen in the discovery of various B cell receptors (BCRs) targeting agents. Bruton's tyrosine kinase (BTK) is one of these recent targets which play a role in the upstream phase of BCR signalling. BTK is an important enzyme that regulates the survival, proliferation, activation and differentiation of B-lineage cells by preventing BCR activation, FC-receptor signalling and osteoclast development. Several BTK inhibitors have been found to be effective against RA during the in vitro and in vivo studies conducted using diverse animal models. 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引用次数: 0
摘要
类风湿性关节炎(RA)是一种复杂的慢性炎症性疾病,影响人体的整个生理机能。它已成为全球致残的主要原因之一。类风湿关节炎的发生和发展涉及个人遗传背景和各种环境因素之间复杂的相互作用。由于这种疾病十分复杂,而且其病理生理机制尚未完全明了,因此要想有效控制 RA,就必须采用多学科方法。在大多数关节炎患者中,异常 B 细胞和自身抗体(主要是抗瓜氨酸肽抗体和类风湿因子)的存在会影响 RA 的进展。因此,靶向 B 细胞的药物现已成为治疗风湿性关节炎的热门话题,这一点从最近发现的各种 B 细胞受体(BCRs)靶向药物的趋势中可见一斑。布鲁顿酪氨酸激酶(BTK)是最近发现的靶点之一,它在BCR信号传导的上游阶段发挥作用。BTK 是一种重要的酶,它通过阻止 BCR 激活、FC 受体信号传导和破骨细胞发育来调节 B 系细胞的存活、增殖、激活和分化。在利用不同动物模型进行的体外和体内研究中,发现了几种 BTK 抑制剂对 RA 有效。本综述重点介绍 BTK 抑制机制及其对免疫介导疾病可能产生的影响,以及目前正在研究的 RA 类型、临床前和临床研究及未来展望。
Therapeutic potential and recent progression of BTK inhibitors against rheumatoid arthritis
Rheumatoid arthritis (RA) is a complex chronic inflammatory illness that affects the entire physiology of human body. It has become one of the top causes of disability worldwide. The development and progression of RA involves a complex interplay between an individual's genetic background and various environmental factors. In order to effectively manage RA, a multidisciplinary approach is required, as this disease is complicated and its pathophysiological mechanism is not fully understood yet. In majority of arthritis patients, the presence of abnormal B cells and autoantibodies, primarily anti-citrullinated peptide antibodies and rheumatoid factor affects the progression of RA. Therefore, drugs targeting B cells have now become a hot topic in the treatment of RA which is quite evident from the recent trends seen in the discovery of various B cell receptors (BCRs) targeting agents. Bruton's tyrosine kinase (BTK) is one of these recent targets which play a role in the upstream phase of BCR signalling. BTK is an important enzyme that regulates the survival, proliferation, activation and differentiation of B-lineage cells by preventing BCR activation, FC-receptor signalling and osteoclast development. Several BTK inhibitors have been found to be effective against RA during the in vitro and in vivo studies conducted using diverse animal models. This review focuses on BTK inhibition mechanism and its possible impact on immune-mediated disease, along with the types of RA currently being investigated, preclinical and clinical studies and future prospective.
期刊介绍:
Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.