Acalabrutinib is a second-generation irreversible inhibitor of BTK (Bruton's tyrosine kinase). The optically pure Acalabrutinib potently inhibits BTK activity with an IC50 of 3 nM (enzymatic assay) and EC50 of 8 nM (human whole-blood CD69 B cell activation assay). Comparing with the first-generation BTK inhibitor Ibrutinib, Acalabrutinib is more selective. The improved selectivity is largely attributed to the reduced intrinsic reactivity of electrophile (Acalabrutinib’s Propiolamide vs Ibrutinib’s acrylamide). As a result, Acalabrutinib was shown to have improved target specificity and in vivo coverage, thus better therapeutic indexes, over Ibrutinib. It displays minimal, or no activities against off-target kinases such as ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1.

Keywords: Acalabrutinib | Supplier | BTK inhibitor | ACP-196 | ACP196 | ACP 196 | CT-ACP196 | CAS [1420477-60-6] | B-Cell transformation | BTK | Inhibitor | Enzymes