| Description: |
In both biochemical and cellular assays, BGB-3111 demonstrates nanomolar Btk inhibition activity. 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 comparison with ibrutinib, BGB-3111 shows much more restricted off-target activities against a panel of kinases, including ITK. BGB-3111 is at least 10-fold weaker than ibrutinib in inhibiting rituximab induced ADCC, consistent with its weak ITK inhibition activity.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. Preliminary 14-day toxicity study in rats shows that BGB-3111 is very well tolerated and maximal tolerate dose (MTD) is not reached when it is dosed up to 250mg/kg/day. |
