ZW-49 

ZW-49 is an orally active pan-EGFR inhibitor with IC₅₀ values at 0.03-1.5 nM. ZW-49 inhibits all subgroups of EGFR mutations with selectivity over wild-type EGFR and other target families. ZW-49 blocks the ATP-binding pocket, occupies a conserved hydrophobic subpocket, avoids steric conflicts with PACC mutation P loops. ZW-49 inhibits cancer cells proliferation, induces G0/G1 phase cell-cycle arrest and apoptosis, and demonstrates anti-proliferative activity in xenograft mice models. ZW-49 can be used for the research of cancer, such as non-small cell lung cancer^[1].

ZW-49 potently inhibits a broad panel of mutant EGFR kinases, including EGFR^L858R/T790M with an IC₅₀ of 1.5 nM, and shows 6.6-fold selectivity over wild-type EGFR (IC₅₀ = 9.9 nM), while also targeting select HER2 mutants^[1].
ZW-49 (72 h) potently inhibits proliferation of EGFR-mutant cell lines, including NCI-H1975 (IC₅₀ = 12 nM) and HCC827 (IC₅₀ = 4 nM), as well as Ba/F3 cells with non-classical EGFR mutations (IC₅₀ = 0.58-5.59 nM), while also inhibits HER2-overexpressing cells^[1].
ZW-49 (1-1000 nM; 2 h) potently and dose-dependently inhibits EGFR phosphorylation and downstream AKT/ERK signaling in EGFR-mutant cell lines, including NCI-H1975, HCC827, and Ba/F3 cells expressing non-classical mutations^[1].
ZW-49 (0.01-1 μM) induces G0/G1 phase cell-cycle arrest and apoptosis in H1975 cell^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ZW-49 (5-25 mg/kg; p.o.; qd; 2 weeks) inhibits tumor growth in various cancer cells xenograft mice models^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

588.66

C₃₃H₃₂N₈O₃

2055109-19-6

C=CC(NC1=CC(N2C(C(C3=CC=CC=C3)=NC4=C2N=C(N=C4)NC5=CC=C(C=C5OC)N6CCN(CC6)C)=O)=CC=C1)=O

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• [1]. Wang C, et al. Design and development of novel EGFR inhibitors spanning all subgroups of EGFR mutations in non-small cell lung cancer[J]. the innovation, 2026.