Targeting Bruton's tyrosine kinase for the treatment of B cell associated malignancies and autoimmune diseases: Preclinical and clinical developments of small molecule inhibitors

Arch Pharm (Weinheim). 2018 Jul;351(7):e1700369. doi: 10.1002/ardp.201700369. Epub 2018 May 9.

Abstract

B cell receptor (BCR) signaling plays a key role in B cell development and function. Aberrant BCR signaling has been confirmed as a central driver for the pathogenesis of various B cell malignancies. Bruton's tyrosine kinase (BTK) is a vital component of BCR signaling and exhibits overexpression in various B cell leukemias and lymphomas. Inhibiting BTK has been proved as an efficient way for B cell malignancy intervention. Remarkable achievements have been made in the pursuit of selective BTK inhibitors, represented by the success of the irreversible BTK inhibitors, ibrutinib and acalabrutinib. Constantly emerging agents exhibiting superior efficacy and safety in preclinical and clinical studies provide promising therapeutics for the treatment of B cell malignancies.

Keywords: BTK inhibitor; Bruton's tyrosine kinase; arthritis; leukemia; lymphoma.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / enzymology
  • Benzamides / adverse effects
  • Benzamides / pharmacology
  • Drug Design*
  • Humans
  • Leukemia, B-Cell / drug therapy
  • Leukemia, B-Cell / enzymology
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / enzymology
  • Piperidines
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Pyrazines / adverse effects
  • Pyrazines / pharmacology
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacology
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazines
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • acalabrutinib
  • Adenine