Zipalertinib — Investigational Agent
EGFR Inhibitor · Phase 2/3 · Taiho Oncology / Cullinan Oncology
Mechanism of Action
Zipalertinib is an orally available, irreversible EGFR tyrosine kinase inhibitor specifically engineered to target EGFR exon 20 insertion mutations. It exhibits a wide therapeutic window by selectively inhibiting mutant EGFR isoforms while demonstrating reduced activity against wild-type EGFR. The molecule forms a covalent bond with the Cys797 residue in the ATP-binding pocket of EGFR. This inhibition prevents downstream signaling through the Ras/Raf/MEK/ERK and PI3K/Akt pathways, which are typically constitutively active in exon 20-mutant cells.
Investigational Indications
- EGFR exon 20 insertion mutant non-small cell lung cancer