Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects

Front. Cell Dev. Biol. 9:630942 DOI: 10.3389/fcell.2021.630942

Understanding of the B-cell receptor signalling pathway led to the identification of a suitable drug target to addresses autoimmunity and inflammation in areas such as MS, RA, pemphigus and SLE. There are currently 22 BTKis in various stages of clinical development. However, AEs such as cardiovascular and bleeding side effects, as well as rash, diarrhoea and infections have been associated with the inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain.Based on clinic...

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June 2019

BTK is involved in both adaptive and innate immune responses and mediates signalling of several immune receptors of relevance to RA and SLE pathogenesis. Targeting BTK is a promising approach therefore for autoimmune disorders with aberrant B cell responses. Evobrutinib is a novel, highly specific, and irreversible BTK inhibitor. In vivo and animal models showed that evobrutinib modulated B cell and innate immune cell activation, was efficacious, and prevented joint damage. The potency of evobru...

January 2014

Ibrutinib is a first-in-class, orally available Btk (Bruton’s tyrosine kinase) inhibitor which has been shown to be effective in the treatment against certain types of leukemia and autoimmune disorders. Btk regulates the expression of genes involved in the differentiation and function of osteoclasts, and therefore inhibiting Btk suppresses osteoclastic bone resorption. Results from in vitro testing showed the suppressive effects on osteoclasts and murine models of RA showed ibrutinib treatment p...

October 2013

Bruton’s tyrosine kinase (BTK) is a part of the cytokine signalling pathways involved in malignancies and autoimmune disorders.. Akinleye et al. provide a review of all the current BTK inhibitors in preclinical and clinical trials for B-cell malignancies and autoimmune disorders, including rheumatoid arthritis. Particular focus is placed on ibrutinib, a novel human BTK-inhibitor, currently in phase III clinical trials. The authors also discuss four new compounds with potential indications in rh...

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