Zanubrutinib

Zanubrutinib (BGB-3111) is a selective and orally active Bruton tyrosine kinase (Btk) inhibitor (IC₅₀: 0.3 nM)^[1][2]. IC50 & Target:BTK^[1] In Vitro:Zanubrutinib (BGB-3111) is a selective Bruton tyrosine kinase (BTK) inhibitor. In both biochemical and cellular assays, Zanubrutinib demonstrates nanomolar BTK inhibition activity. In several MCL and DLBCL cell lines, Zanubrutinib inhibits BCR aggregation-triggered BTK autophosphorylation, blocks downstream PLC-γ2 signaling, and potently inhibits cell proliferation. In comparison with PCI-32765, Zanubrutinib shows much more restricted off-target activities against a panel of kinases, including ITK^[1]. In Vivo:Zanubrutinib (BGB-3111) induces dose-dependent anti-tumor effects against REC-1 MCL xenografts engrafted either subcutaneously or systemically via tail vein injection in mice. In the subcutaneous xenografts, Zanubrutinib at 2.5 mg/kg BID shows similar activity as PCI-32765 at 50 mg/kg QD. In the systemic model, the median survival of Zanubrutinib 25 mg/kg BID group is significantly longer than those of both PCI-32765 50 mg/kg QD and BID groups. In an ABC-subtype DLBCL (TMD-8) subcutaneous xenograft model, Zanubrutinib also demonstrates better anti-tumor activity than PCI-32765. Preliminary 14-day toxicity study in rats shows that Zanubrutinib is very well tolerated and maximal tolerate dose (MTD) is not reached when it is dosed up to 250 mg/kg/day^[1].