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Development of BTK inhibitors for the treatment of B-cell malignancies

  • Hyung-Ook KimEmail author
Review
  • 137 Downloads

Abstract

BTK is a key component of B-cell receptor signaling and functions as an important regulator of cell proliferation and survival in B-cell malignancies. The first-in-class BTK inhibitor ibrutinib is a small molecule drug that binds covalently to BTK and has been proved to be an effective treatment for various B-cell malignancies. However, it has off-target activities on non-BTK kinases that are related to side effects or might be translated into clinical limitations, with resistance to ibrutinib also reported. Much progress has been made in the development of more selective and second-generation BTK inhibitors. A recent shift in the mechanisms of action of BTK inhibitors is noteworthy, and novel inhibitors acting through noncovalent BTK inhibition are now being developed. This review describes key characteristics of ibrutinib, including current issues of its clinical use, and summarizes preclinical properties and clinical developments of second-generation BTK inhibitors for the treatment of B-cell malignancies. A review of novel noncovalent BTK inhibitors are also included.

Keywords

BTK B-cell malignancies Ibrutinib BTK inhibitors Noncovalent BTK inhibitors 

Notes

Acknowledgements

There was no funding source for this work.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest.

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Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.Department of Clinical Medicinal SciencesKonyang UniversityNonsanRepublic of Korea

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