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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. 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). It preferentially targets cells expressing EGFRT790M over those expressing EGFR without the T790M mutation. WZ4002 is also bioavailable in vivo when given intravenously and is effective in mouse models of lung cancer driven by EGFRT790M. Efficacy may be enhanced when used in combination therapy with inhibitors of Met kinase activity, Bcl-2, or histone deacetylases.Formal Name: N-[3-[[5-chloro-2-[[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]amino]-4-pyrimidinyl]oxy]phenyl]-2-propenamide. CAS Number: 1213269-23-8. Molecular Formula: C25H27ClN6O3. Formula Weight: 495.0. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 50 mg/ml, DMSO: 50 mg/ml, Ethanol: 1 mg/ml. lambdamax: 279 nm. SMILES: CN1CCN(C2=CC=C(NC3=NC=C(Cl)C(OC4=CC=CC(NC(C=C)=O)=C4)=N3)C(OC)=C2)CC1. InChi Code: InChI=1S/C25H27ClN6O3/c1-4-23(33)28-17-6-5-7-19(14-17)35-24-20(26)16-27-25(30-24)29-21-9-8-18(15-22(21)34-3)32-12-10-31(2)11-13-32/h4-9,14-16H,1,10-13H2,2-3H3,(H,28,33)(H,27,29,30). InChi Key: ITTRLTNMFYIYPA-UHFFFAOYSA-N.
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