acalabrutinib-acp-196

Description: Acalabrutinib (also known as ACP-196; trade name: Calquence) is a selective second-generation Bruton’s tyrosine kinase (BTK) inhibitor, which prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. In 2017, Acalabrutinib was approved by FDA to treat adults with mantle cell lymphoma. Previous study showed that ACP-196 had high selectivity for Btk when tested against a panel of 395 non-mutant kinases, which was associated with the reduced intrinsic reactivity of ACP-196's electrophile. Moreover, ACP-196 could not inhibit EGFR, Itk or Txk, which is unlike ibrutinib. In addition, the phosphoflow assays on EGFR expressing cell lines furthre confirmed ibrutinib's EGFR inhibition without inhibition observed for ACP-196.

References: J Hematol Oncol. 2016 Mar 9; 9:21; Cancer Res. 2015, 75 (15 Supplement):2596