Bruton's tyrosine kinase: A promising target for treating systemic lupus erythematosus.

Int Immunopharmacol

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address:

Published: December 2024

AI Article Synopsis

  • Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting various organs, where autoreactive B cells play a key role by producing harmful autoantibodies.
  • Researchers are exploring small molecule inhibitors targeting Bruton's tyrosine kinase (BTK) as a promising treatment strategy, which may be more effective than current biologic agents.
  • While initial studies in lupus-prone mice show potential for BTK inhibitors, clinical trials have encountered issues with effectiveness and safety, highlighting the need for improved inhibitors in future research.

Article Abstract

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disorder involving multiple organs and systems. There is growing evidence that autoreactive B cells occupy a central role in the occurrence and progression of SLE due to their ability to generate pathogenic autoantibodies. Small molecule inhibitors targeting Bruton's tyrosine kinase (BTK), a crucial intracellular kinase regulating B cell development and function, emerge as a new strategy to treat SLE in recent years and are superior to biologic agents depleting B cells in many aspects. Supportive data obtained from lupus-prone mice preliminarily demonstrated the promising therapeutic potential of BTK inhibition. However, these BTK inhibitors, including elsubrutinib, evobrutinib, etc., mostly face with unsatisfactory efficacy and certain safety issues during clinical use, driving the quest for new-generation inhibitors with improved potency and higher selectivity. This paper elaborates the importance of BTK involvement in SLE pathogenesis, reviews the clinical research progress of BTK inhibitors for SLE and discusses limitations and challenges the drugs met in development, in order to contribute to a deeper understanding of disease mechanism and provide a reference for new-generation BTK inhibitor research.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2024.113040DOI Listing

Publication Analysis

Top Keywords

bruton's tyrosine
8
tyrosine kinase
8
systemic lupus
8
lupus erythematosus
8
btk inhibitors
8
btk
6
sle
5
kinase promising
4
promising target
4
target treating
4

Similar Publications

Purpose: Venetoclax and Bruton's tyrosine kinase inhibitors (BTKis) are key treatment options for patients with chronic lymphocytic leukemia (CLL) in the frontline setting. This study characterized postdiscontinuation treatment patterns and hospitalization of frontline venetoclax and BTKis in a national sample of older adults with CLL.

Methods: We identified 1,770 Medicare beneficiaries 66 years and older with CLL initiating venetoclax with obinutuzumab (VEN-O, n = 193) or BTKi treatment (n = 1,577) in the frontline setting between June 01, 2019, and June 30, 2020.

View Article and Find Full Text PDF

Bruton's tyrosine kinase inhibitors (BTKis) exhibit significant interindividual pharmacokinetics, making therapeutic drug monitoring (TDM) a promising approach for personalized therapy. However, simultaneous quantification of multiple BTKis poses technical challenges. A unified protocol for BTKis detection would be clinically desirable.

View Article and Find Full Text PDF

Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression.

View Article and Find Full Text PDF

Background: Primary central nervous system lymphoma (CNSL) is a rare, aggressive non-Hodgkin lymphoma confined to the CNS. Although radiation and chemotherapy, particularly high-dose methotrexate (HD-MTX), are effective treatments, the relapse rates remain high, prompting the exploration of novel therapeutic options. Ibrutinib, an irreversible Bruton tyrosine kinase (BTK) inhibitor, has shown promise in various B-cell malignancies, including CNSL.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!