产品描述:
The recurrent missense mutation T790M in the kinase domain of epidermal growth factor receptor (EGFR) is a gatekeeper mutation, as it sterically hinders binding of inhibitors while preserving catalytic activity.{27827,27829} WZ4002 is an irreversible EGFR tyrosine kinase inhibitor that blocks ATP-dependent autophosphorylation of EGFR carrying the T790M mutation as well as an L858R mutation (IC50 = 8 nM).{27829,27826} It preferentially targets cells expressing EGFRT790M over those expressing EGFR without the T790M mutation.{27829} WZ4002 is also bioavailable in vivo when given intravenously and is effective in mouse models of lung cancer driven by EGFRT790M.{27829} Efficacy may be enhanced when used in combination therapy with inhibitors of Met kinase activity, Bcl-2, or histone deacetylases.{27825,27822,27824,27823}