DZD9008 (Sunvozertinib) is an oral, potent, irreversible, wild type-selective EGFR inhibitor against EGFR or HER2 Exon20ins and other mutations (IC50=0.4-2.1 nM).
DZD9008 downregulates pEGFR with IC50 ranging from 1 to 22 nM in a panel of tumor cell lines expressing EGFR L858R, Exon19del, L858R/T790M, various Exon20ins or uncommon mutations.
DZD9008 shows similary potency against pHER2 in tumor cells with HER2 Exon20ins mutation, with IC50 of 7 nM.
DZD9008 is less potent in modulating pEGFR in tumor cells expressing wild type EGFR (IC50>80 nM).
DZD9008 suppressed cell proliferation with GI50 of 1 to 60 nM in tumor cells carrying EGFR L858R, Exon19del, L858R/T790M, various Exon20ins or uncommon mutations in cell proliferation assays.
DZD9008 exhibits tumor growth inhibition and regression in CDX and PDX models carrying EGFR Exon19del single mutation, L858R/T790M double mutations, and PDX models harboring G719S/L861Q or Exon20ins.