Zanubrutinib (BGB-3111)是一种有效的、特异的不可逆性型BTK抑制剂，对其他激酶如ITK、JAK3和EGFR仅具有微弱的脱靶抑制效应。 Information Zanubrutinib (BGB-3111) Zanubrutinib (BGB-3111) is a potent, specific and irreversible BTK inhibitor that has been shown to have a lower off-target inhibitory activity on other kinases, including ITK, JAK3 and EGFR. Targets BTK (Cell-free assay) In vitro In biochemical and cellular assays, BGB-3111 is more selective than ibrutinib for BTK vs. EGFR, FGR, FRK, HER2, HER4, ITK, JAK3, LCK, BLK and TEC. In several MCL and DLBCL cell lines, BGB-3111 inhibits BCR aggregation-triggered BTK autophosphorylation, blocks downstream PLC-γ2 signaling, and potently inhibits cell proliferation. In vivo In preclinical animal studies, BGB-3111 demonstrates superior oral bioavailability, achieving higher exposure and more complete target inhibition in the tissues than ibrutinib. In mouse BTK occupancy assays, treatment with BGB-3111 results in a dose-dependent BTK occupancy and shows about 3-fold more potency than ibrutinib in target organs, including PBMC and spleen. Both in the REC-1 MCL and ABC subtype DLBCL (TMD-8) xenograft models, BGB-3111 induces dose-dependent anti-tumor effects and demonstrates superior efficacy in comparison with ibrutinib. Toxicity study in rats indicates that BGB-3111 is very well tolerated, and the MTD is not reached when it is dosed up to 250 mg/kg/day.