9KL4

Crystal structure of EGFR complexed with N-[4-[4-amino-6-ethynyl-5-(3-quinolyl)pyrrolo[2,3-d]pyrimidin-7-yl]norbornan-1-yl]pyrimidine-5-carboxamide

This is a non-PDB format compatible entry.

Summary for 9KL4

• Entry DOI: 10.2210/pdb9kl4/pdb
• Descriptor: Epidermal growth factor receptor, N-[4-[4-amino-6-ethynyl-5-(3-quinolyl)pyrrolo[2,3-d]pyrimidin-7-yl]norbornan-1-yl]pyrimidine-5-carboxamide, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: tki, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 38115.46

Authors

Suzuki, T.,Kasuga, H.,Yamamoto, F. (deposition date: 2024-11-14, release date: 2025-09-24, Last modification date: 2026-05-27)

Primary citation

Kasuga, H.,Kataoka, Y.,Yamamoto, F.,Miyamoto, R.,Tsuji, S.,Suzuki, T.,Mizuarai, S.
TAS3351 is a brain penetrable EGFR-TKI that overcomes T790M and C797S resistant mutations.
Commun Med (Lond), 6:-, 2026

PubMed Abstract: Activating mutations in the epidermal growth factor receptor (EGFR), particularly exon 19 deletions and L858R mutation, are frequently observed in non-small cell lung cancer (NSCLC) and confer sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Among these EGFR-TKIs, osimertinib is currently the standard of care for patients with NSCLC harboring the activating mutations. However, resistant mutations often arise, leading to resistance to osimertinib. The resistant mutation that most frequently occurs in EGFR during osimertinib treatment is the C797S mutation. Another major resistant mutation arising in EGFR during treatment with other EGFR-TKIs, such as gefitinib and afatinib, is the T790M mutation. Currently, no approved EGFR-TKIs are effective in patients who simultaneously develop the T790M and C797S mutations. Additionally, brain metastasis often causes disease progression due to reduced drug penetration into the brain.

PubMed: 41882274
DOI: 10.1038/s43856-026-01546-1

Experimental method

X-RAY DIFFRACTION (2.32 Å)