HZ-A-005，一种在临床前研究中具有强大、选择性和共价结合特性的布鲁顿酪氨酸激酶抑制剂。
HZ-A-005, a potent, selective, and covalent Bruton's tyrosine kinase inhibitor in preclinical development.
机构信息
Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou 310013, China.
Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou 310013, China.
出版信息
Bioorg Chem. 2020 Dec;105:104377. doi: 10.1016/j.bioorg.2020.104377. Epub 2020 Oct 13.
Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec kinases family and is essential for B cell receptor (BCR) mediated signaling. BTK inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies. Here we disclose a potent, selective, and covalent BTK inhibitor, HZ-A-005, currently in preclinical development. HZ-A-005 demonstrated dose-dependent activity in two xenograft models of lymphoma in vivo. It showed highly favourable safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles in preclinical studies. On the basis of its potency, selectivity, and covalent mode of inhibition, HZ-A-005 reveals the potential to be a promising BTK inhibitor for a wide range of cancer indications.
布鲁顿酪氨酸激酶（BTK）是一种非受体酪氨酸激酶，属于 Tec 激酶家族成员，是 B 细胞受体（BCR）介导的信号转导所必需的。BTK 抑制剂如伊布替尼在治疗 B 细胞恶性肿瘤方面发挥着重要作用。我们在此披露了一种正在临床前开发的强效、选择性和共价 BTK 抑制剂 HZ-A-005。HZ-A-005 在体内两种淋巴瘤异种移植模型中表现出剂量依赖性活性。它在临床前研究中表现出高度有利的安全性、药代动力学（PK）和药效学（PD）特征。基于其效力、选择性和共价抑制模式，HZ-A-005 显示出作为广泛癌症适应症的有前途的 BTK 抑制剂的潜力。
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