Kinase inhibitor: BTK (highly selective). Limits 'cytokine storm' in humans. AstraZeneca, Apr 14 2020, https://www.astrazeneca.com/media-centre/press-releases/2020/astrazeneca-initiates-calavi-clinical-trial-with-calquence-against-covid-19.html.
Biochemicals & reagents
1) Wu et al. (2016), Acalabrutinnib (ACP-196): a second-generation BTK inhibitor; J. Hematol. Oncol. 9 21 2) Barf et al. (2017), Acalabrutinib (ACP-196): A covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile; J. Pharmacol. Exp. Ther. 363 240 3) Herman et al. (2017), The Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse models of chronic lymphocytic leukemia; Clin. Cancer Res. 23 2831 4) Weber, et al. (2017), Weber et al. (2017), Bruton’s Tyrosine Kinase: An Emerging Key Player in Innate Immunity; Front. Immunol. 8 1454
Acalabrutinib (1420477-60-6) is a highly selective, potent (IC50 = 3nM), and irreversible inhibitor of Bruton’s tyrosine kinase (BTK) (1). The number of serious side effects observed with Ibrutinib were decreased by improved target selectivity (especially against TEC family kinases and EGFR) (2). This compound also significantly inhibits BCR signaling, inhibits tumor proliferation, and reduces tumor burden (3) and is a clinically useful agent for treating B-cell cancers. BTK has also been shown to have a role in modulating the innate immune system, especially in dendritic cells and macrophages, suggesting a possible role in immunotherapy (4).