Zanubrutinib is a potent and covalent inhibitor of Bruton's tyrosine kinase (BTK; IC50 = 0.3 nM).1 It is selective for BTK over a panel of 304 kinases at 1 μM but does inhibit EGFR, Tec, Blk, BMX, HER4, and TXK (IC50s = 0.62-33 nM). Zanubrutinib inhibits phosphorylation of BTK at Y233 (IC50 = 1.8 nM) in Ramos cells and reduces viability of REC-1 cells (IC50 = 0.36 nM). In vivo, zanubrutinib (2.5 and 7.5 mg/kg) reduces tumor volume in an OCI-LY10 diffuse large B cell lymphoma (DLBCL) mouse xenograft model.
1.Guo, Y., Liu, Y., Hu, N., et al.Discovery of zanubrutinib (BGB-3111), a novel, potent, and selective covalent inhibitor of bruton's tyrosine kinaseJ. Med. Chem.62(17)7923-7940(2019)