BTK binds BTK inhibitors

Stable Identifier
R-HSA-9691421
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Tyrosine-protein kinase BTK (aka Bruton Tyrosine Kinase) is essential for B-cell development and differentiation, and in B-cell receptor signalling. It plays an important role in the function of immune cells of innate and adaptive immunity. BTK inhibitors prevent the proliferation, trafficking, chemotaxis and adhesion of B cells. BTK is also a driving force for chronic lymphocytic leukemia (CLL) and other B cell malignancies.

Ibrutinib is a first-in-class BTK inhibitor that irreversibly binds to Cys-481 in BTK's kinase domain and potently blocks its enzymatic activity (Ponader et al. 2012). It is used to treat CLL and mantle cell lymphoma (MCL).

Acalabrutinib, a second-generation BTK inhibitor, is used for the treatment of CCL (Byrd et al. 2015) and MCL (Cheah et al. 2016). It is in clinical trial in COVID-19 patients as part of the UK's ACCORD initiative. Preliminary data from off-label use in the US suggests that acalabrutinib therapy normalises inflammatory markers such as CRP and IL6 in patients with severe COVID-19. Targeting host hyperinflammation via BTK inhibition may be a rational therapeutic strategy that may improve patient outcomes in this disease (Roschewski et al. 2020).

Other BTK inhibitors which target BTK include spebrutinib, tirabrutinib, naquotinib and zanubrutinib (Tanaka et al. 2020).

Literature References
PubMed ID Title Journal Year
22180443 The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo

Chiorazzi, N, Chen, SS, Wierda, WG, Gandhi, V, Ponader, S, Keating, MJ, Buggy, JJ, Balakrishnan, K, Burger, JA, O'Brien, S

Blood 2012
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