Acalabrutinib | Highly selective BTK inhibitor

Acalabrutinib (1420477-60-6) is a highly selective, potent (IC₅₀ = 3 nM), and irreversible inhibitor of Bruton’s tyrosine kinase (BTK).¹ Improved target selectivity (especially against TEC family kinases and EGFR) decreased the number of serious side effects observed with Ibrutinib.² Acalabrutinib significantly inhibits BCR signaling, inhibits tumor proliferation, and reduces tumor burden.³ 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

References/Citations:

1) Wu et al. (2016), Acalabrutinib (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), Bruton’s Tyrosine Kinase: An Emerging Key Player in Innate Immunity; Front. Immunol. 8 1454