2. Academic Validation
  3. Progress in the development of small molecular inhibitors of the Bruton's tyrosine kinase (BTK) as a promising cancer therapy

Progress in the development of small molecular inhibitors of the Bruton's tyrosine kinase (BTK) as a promising cancer therapy

  • Bioorg Med Chem. 2021 Oct 1:47:116358. doi: 10.1016/j.bmc.2021.116358.
Xiu-Juan Liu 1,  Xu-Liu 1,  Xiao-Jing Pang 1,  Xin -Ying Yuan 1,  Guang-Xi Yu 2,  Yin-Ru Li 2,  Yong-Feng Guan 1,  Yan-Bing Zhang 1,  Jian Song 3,  Qiu-Rong Zhang 4,  Sai-Yang Zhang 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Institute of Drug Discovery & Development, Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Zhengzhou University, Zhengzhou 450001, China.
  • 2 School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 3 School of Pharmaceutical Sciences, Institute of Drug Discovery & Development, Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Zhengzhou University, Zhengzhou 450001, China; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address: [email protected].
  • 4 School of Pharmaceutical Sciences, Institute of Drug Discovery & Development, Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Zhengzhou University, Zhengzhou 450001, China. Electronic address: [email protected].
  • 5 School of Pharmaceutical Sciences, Institute of Drug Discovery & Development, Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Zhengzhou University, Zhengzhou 450001, China; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China; Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001, China. Electronic address: [email protected].
PMID: 34479103 DOI: 10.1016/j.bmc.2021.116358
Abstract

Bruton tyrosine kinase (Btk) is a key kinase in the B cell antigen receptor signal transduction pathway, which is involved in the regulation of the proliferation, differentiation and Apoptosis of B cells. Btk has become a significant target for the treatment of hematological malignancies and autoimmune diseases. Ibrutinib, the first-generation Btk Inhibitor, has made a great contribution to the treatment of B cell malignant tumors, but there are still some problems such as resistance or miss target of site mutation. Therefore, there is an imperative need to develop novel Btk inhibitors to overcome these problems. Besides, proteolysis targeting chimera (PROTAC) technology has been successfully applied to the development of Btk degradation agents, which has opened a fresh way for the Btk targeted treatment. This paper reviews the biological function of Btk, the discovery and development of Btk targeted drugs as a promising Cancer therapy. It mainly reviews the binding sites and structural characteristics of Btk, structure-activity relationships, activity and drug resistance of Btk inhibitors, as well as potential treatment strategies to overcome the resistance of Btk, which provides a reference for the rational design and development of new powerful Btk inhibitors.

Keywords

Anticancer activity; Bruton tyrosine kinase; Inhibitors; PROTAC.

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