9QXN
Crystal Structure of wild-type EGFR in complex with the reversible inhibitor Sevabertinib (BAY 2927088)
This is a non-PDB format compatible entry.
Summary for 9QXN
| Entry DOI | 10.2210/pdb9qxn/pdb |
| Descriptor | Epidermal growth factor receptor, SUCCINIC ACID, CHLORIDE ION, ... (7 entities in total) |
| Functional Keywords | kinase, inhibitor, complex, reversible, cancer, hydrolase-hydrolase inhibitor complex, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 40545.57 |
| Authors | Hillig, R.C. (deposition date: 2025-04-16, release date: 2025-10-15, Last modification date: 2026-01-21) |
| Primary citation | Siegel, F.,Siegel, S.,Kotynkova, K.,Karsli Uzunbas, G.,Korr, D.,Tomono, H.,Andersen, S.,Denney, D.,Berger, M.,Schulze, V.K.,Lewis, T.A.,Kaplan, B.,Golfier, S.,Mortier, J.,Hillig, R.C.,Boemer, U.,Petersen, K.,Eis, K.,Williams, S.,Ruttinger, D.,Cherniack, A.D.,Loong, H.H.,Goto, K.,Grassi, P.,Meyerson, M.,Greulich, H. Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer. Cancer Discov, 16:81-94, 2026 Cited by PubMed Abstract: Exon 20 insertions of HER2, encoded by ERBB2, and other activating HER2 mutations occur in 2-4% of lung adenocarcinomas, but there are only limited therapeutic options available for these patients. Sevabertinib (BAY 2927088) is a potent and reversible dual EGFR-HER2 inhibitor that is selective with respect to wild-type EGFR. Here, we report the preclinical activity of sevabertinib in lung cancer models harboring alterations of HER2, including exon 20 insertions, point mutations, and amplification of wild-type ERBB2. We furthermore demonstrate the activity of sevabertinib in a cancer cell line dependent on a fusion of NRG1, a ligand for the HER2 family member and heterodimerization partner, HER3. Finally, we report patient responses to sevabertinib from a Phase 1/2 clinical trial, indicating potential benefit for patients with HER2-mutant lung cancer. PubMed: 41090369DOI: 10.1158/2159-8290.CD-25-0605 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.142 Å) |
Structure validation
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