9DF2

EGFR Exon20 insertion mutant ASV bound with (S)-3-((3-chloro-2-methoxyphenyl)amino)-2-(3-((tetrahydrofuran-2-yl)methoxy)pyridin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one

This is a non-PDB format compatible entry.

Summary for 9DF2

• Entry DOI: 10.2210/pdb9df2/pdb
• Descriptor: Epidermal growth factor receptor, 3-[(3-chloranyl-2-methoxy-phenyl)amino]-2-[3-[[(2S)-oxolan-2-yl]methoxy]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: kinase, inhibitor, oncoprotein, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 39171.95

Authors

Hilbert, B.J. (deposition date: 2024-08-29, release date: 2025-05-14, Last modification date: 2025-06-11)

Primary citation

Pagliarini, R.A.,Henderson, J.A.,Milgram, B.C.,Borrelli, D.R.,Brooijmans, N.,Hilbert, B.J.,Huff, M.R.,Ito, T.,Kryukov, G.V.,Ladd, B.,Martin, B.R.,Motiwala, H.,O'Hearn, E.,Tsai, C.F.,Wang, W.,Bellier, J.,Boland, L.,Clark, S.,Hensley, E.,Hata, A.N.,Kuzmic, P.,Guzman-Perez, A.,Jackson, E.L.,Stuart, D.D.
STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20-Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models.
Clin.Cancer Res., :OF1-OF17, 2025

PubMed Abstract: Commonly occurring oncogenic mutations in EGFR render non-small cell lung cancers sensitive to approved EGFR-targeted drugs. EGFR in-frame exon 20 insertion (ex20ins) mutants are, however, less sensitive to such drugs. The efficacy of existing medicines may in part be limited by their selectivity for ex20ins mutations relative to wild-type EGFR, which is important for epithelial tissue homeostasis.

PubMed: 40465424
DOI: 10.1158/1078-0432.CCR-24-3833

Experimental method

X-RAY DIFFRACTION (2.5 Å)