Discovery of selective irreversible inhibitors of B-Lymphoid tyrosine kinase (BLK)

B-lymphoid tyrosine kinase (BLK), a member of the SRC family nonreceptor tyrosine kinase, is involved in the B-cell receptor (BCR) signaling pathway and B cell development and function. Dysregulation of BLK is associated with autoimmune diseases and cancer. However, there is an absence of good tool compounds for BLK, and the molecular mechanisms by which BLK mediates physiological and pathological processes are poorly understood. Herein, we present the discovery of a novel series of selective and irreversible inhibitors of BLK with nanomolar potency against BLK in biochemical and cellular assays. Compound 25 demonstrated potent antiproliferative activities against several B cell lymphoma cell lines. These compounds constitute the first series of selective inhibitors developed for BLK and could help expedite the exploration of BLK functions.(c) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

In this study, a novel series of selective and irreversible inhibitors of BLK were discovered, showing potent antiproliferative activities against several B-cell lymphoma cell lines. These compounds represent the first selective inhibitors developed for BLK, which could expedite the exploration of BLK functions.