HZ-A-005, a potent, selective, and covalent Bruton's tyrosine kinase inhibitor in preclinical development

  • Bioorg Chem. 2020 Dec;105:104377. doi: 10.1016/j.bioorg.2020.104377.
Wenhai Huang  1 ,  Shu Wang  1 ,  Zhimin Zhang  1 ,  Chixiao Zhang  1 ,  Shenxin Zeng  1 ,  Meihao Liang  1 ,  Zhengrong Shen  2 ,  Xingguo Liu  3
Affiliations
  • 1. Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou 310013, China.
  • 2. Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou 310013, China. Electronic address: [email protected].
  • 3. Hangzhou Hertz Pharmaceutical Co., Hangzhou 310018, China. Electronic address: [email protected].
PMID: 33091668 DOI: 10.1016/j.bioorg.2020.104377
Abstract

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.

Keywords
Anti-proliferative activity; BTK; HZ-A-005; Preclinical studies; Safety; Stability.
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