HBE-843, a Novel, Potent, and Selective EGFR Targeting PROTAC for the Treatment of Non-Small-Cell Lung Cancer.
1/5 보강
The emergence of the EGFR C797S mutation poses a significant challenge in the treatment of non-small cell lung cancer due to resistance to third-generation EGFR-tyrosine kinase inhibitors.
APA
Baig MH, Kim CJ, et al. (2026). HBE-843, a Novel, Potent, and Selective EGFR Targeting PROTAC for the Treatment of Non-Small-Cell Lung Cancer.. Archiv der Pharmazie, 359(2), e70193. https://doi.org/10.1002/ardp.70193
MLA
Baig MH, et al.. "HBE-843, a Novel, Potent, and Selective EGFR Targeting PROTAC for the Treatment of Non-Small-Cell Lung Cancer.." Archiv der Pharmazie, vol. 359, no. 2, 2026, pp. e70193.
PMID
41635121 ↗
Abstract 한글 요약
The emergence of the EGFR C797S mutation poses a significant challenge in the treatment of non-small cell lung cancer due to resistance to third-generation EGFR-tyrosine kinase inhibitors. This study introduces a novel and highly selective EGFR PROTAC, HBE-843, designed to degrade mutant EGFR while sparing wild-type EGFR. Our degrader not only effectively degrades the L858R but also shows promising activity against exon 19 deletion, T790M, and C797S, where it demonstrated low nanomolar GI (26-103 nM) across all these EGFR mutant-harboring cell lines while sparing the wild-type. HBE-843 effectively reduced EGFR protein levels in mutant cells in a dose-dependent manner, with a DC in the low nanomolar range (1.9-18 nM) and a D above 90%. Mechanistic studies showed that HBE-843 mediates EGFR degradation through the CRBN-associated proteasome pathway, preventing the activation of the ERK downstream signal and hindering cell growth. In vivo studies demonstrated a 112% tumor growth inhibition in L858R-induced cancers. These findings suggest that HBE-843 holds promise as a lead compound for developing new drugs to overcome C797S mutant-mediated resistance in clinical settings.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- ErbB Receptors
- Lung Neoplasms
- Carcinoma
- Non-Small-Cell Lung
- Antineoplastic Agents
- Animals
- Dose-Response Relationship
- Drug
- Protein Kinase Inhibitors
- Cell Proliferation
- Structure-Activity Relationship
- Mice
- Cell Line
- Tumor
- Drug Screening Assays
- Antitumor
- Mutation
- Molecular Structure
- Nude
- Xenograft Model Antitumor Assays
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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