Acalabrutinib, Free Base

Soluble in DMSO. Acalabrutinib, also known as ACP-196, is an irreversible Bruton tyrosine kinase (BTK) inhibitor. It binds covalently to Cys481 with improved selectivity and in vivo target coverage. Acalabrutinib inhibited BTK with an IC50 of 3 nM and had improved target specificity over ibrutinib with 323-, 94-, 19-, and 9-fold selectivity over the other TEC kinase family members (ITK, TXK, BMX, and TEC, respectively) and no activity against EGFR. Wu J., et al. 'Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor.' J. Hematol. Oncol. 9: 21 (2016). Acalabrutinib avoided major platelet dysfunction in non-Hodgkin lymphoma (NHL) patients associated with ibrutinib treatment. Bye A.P., et al. 'Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib. Blood Adv. 1: 2610-2623 (2017). In an uncontrolled, phase 1-2, multicenter study, the selective and irreversible BTK inhibitor acalabrutinib demonstrated promising safety and efficacy profiles in patients with relapsed chronic lymphocytic leukemia (CLL), including those with chromosome 17p13.1 deletion. Byrd J.C., et al. 'Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.' N. Engl. J. Med. 374: 323-332 (2016).