BTK inhibitors: past, present, and future

Trends Pharmacol Sci. 2024 Aug;45(8):691-707. doi: 10.1016/j.tips.2024.06.006. Epub 2024 Jul 17.

Abstract

Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the treatment landscape for B cell lymphomas such as chronic lymphocytic leukemia (CLL). The first-in-class BTK inhibitor ibrutinib has recently been succeeded by covalent BTK inhibitors that are safer but still face challenges of resistance mutations. The noncovalent BTK inhibitor pirtobrutinib was recently approved for relapsed and refractory CLL, and whether noncovalent BTK inhibitors will supplant covalent BTK inhibitors as upfront treatment options either alone or in combination will be determined. Meanwhile, newer BTK inhibitors and BTK degraders are vying for their place in the potential future landscape of B cell cancers as well as autoimmune diseases. This review will cover the latest progress in BTK inhibitor development and where the field is moving in light of these recent discoveries.

Keywords: BTK inhibitor; Bruton’s tyrosine kinase; degrader; novel therapy; resistance mechanisms; small molecule inhibitor.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase* / antagonists & inhibitors
  • Agammaglobulinaemia Tyrosine Kinase* / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Protein Kinase Inhibitors* / pharmacology
  • Protein Kinase Inhibitors* / therapeutic use

Substances

  • Agammaglobulinaemia Tyrosine Kinase
  • Protein Kinase Inhibitors
  • BTK protein, human
  • Antineoplastic Agents