BTK binds BTK inhibitors

Tyrosine-protein kinase BTK (aka Bruton Tyrosine Kinase) is essential for B-cell development and differentiation, and in B-cell receptor signalling. It plays an important role in the function of immune cells of innate and adaptive immunity. BTK inhibitors prevent the proliferation, trafficking, chemotaxis and adhesion of B cells. BTK is also a driving force for chronic lymphocytic leukemia (CLL) and other B cell malignancies.<br><br>Ibrutinib is a first-in-class BTK inhibitor that irreversibly binds to Cys-481 in BTK's kinase domain and potently blocks its enzymatic activity (Ponader et al. 2012). It is used to treat CLL and mantle cell lymphoma (MCL).<br><br>Acalabrutinib, a second-generation BTK inhibitor, is used for the treatment of CCL (Byrd et al. 2015) and MCL (Cheah et al. 2016). It is in clinical trial in COVID-19 patients as part of the UK's ACCORD initiative. Preliminary data from off-label use in the US suggests that acalabrutinib therapy normalises inflammatory markers such as CRP and IL6 in patients with severe COVID-19. Targeting host hyperinflammation via BTK inhibition may be a rational therapeutic strategy that may improve patient outcomes in this disease (Roschewski et al. 2020).<br><br>Other BTK inhibitors which target BTK include spebrutinib, tirabrutinib, naquotinib and zanubrutinib (Tanaka et al. 2020).

酪氨酸蛋白激酶BTK（又称布鲁顿酪氨酸激酶）对于B细胞的发育和分化至关重要，并在B细胞受体信号传导中发挥着重要作用。它在先天性和适应性免疫细胞的机能中扮演着关键角色。BTK抑制剂能够阻止B细胞的增殖、迁移、趋化性和粘附。BTK也是慢性淋巴细胞白血病（CLL）及其他B细胞恶性肿瘤的推动力。<br><br>伊布替尼作为首个BTK抑制剂，能够不可逆地与BTK激酶域中的Cys-481结合，并强力阻断其酶活性（Ponader等，2012年）。它被用于治疗CLL和套细胞淋巴瘤（MCL）。<br><br>阿卡布拉汀是第二代BTK抑制剂，用于治疗CCL（Byrd等，2015年）和MCL（Cheah等，2016年）。它是英国ACCORD计划的一部分，在COVID-19患者中进行临床试验。美国非适应症使用的初步数据显示，阿卡布拉汀治疗可恢复正常炎症标志物，如C反应蛋白（CRP）和白细胞介素6（IL6）的水平，在重症COVID-19患者中。通过BTK抑制宿主过度炎症可能是一种合理的治疗策略，有助于改善该疾病患者的预后（Roschewski等，2020年）。<br><br>其他针对BTK的BTK抑制剂还包括斯佩布鲁汀、提拉布汀、纳奎汀和扎努布汀（Tanaka等，2020年）。