Department of Pharmaceutical Chemistry, DPSRU, New Delhi, India.
Department of Pharmaceutical Chemistry, SPER, Jamia Hamdard, New Delhi, India.
Chem Biol Drug Des. 2024 Jul;104(1):e14582. doi: 10.1111/cbdd.14582.
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.
类风湿关节炎（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。它已成为全球导致残疾的主要原因之一。RA 的发展和进展涉及个体遗传背景和各种环境因素之间的复杂相互作用。为了有效管理 RA，需要采用多学科方法，因为这种疾病很复杂，其病理生理机制尚未完全了解。在大多数关节炎患者中，异常 B 细胞和自身抗体的存在，主要是抗瓜氨酸肽抗体和类风湿因子，会影响 RA 的进展。因此，针对 B 细胞的药物已成为 RA 治疗的热门话题，这从最近发现的各种针对 B 细胞受体（BCR）的靶向药物的趋势中可以明显看出。布鲁顿酪氨酸激酶（BTK）是最近的一个靶点，它在 BCR 信号转导的上游阶段发挥作用。BTK 是一种重要的酶，通过阻止 BCR 激活、Fc 受体信号转导和破骨细胞发育，调节 B 细胞谱系细胞的存活、增殖、激活和分化。在使用不同动物模型进行的体外和体内研究中，已经发现几种 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性疾病的可能影响，以及目前正在研究的 RA 类型、临床前和临床研究以及未来的展望。
