Orthoallosteric EGFR‐TKIs: A New Paradigm in NSCLC Treatment Strategy Targeting the C797S Mutation DOI Open Access
Iqrar Ahmad, Harun Patel

Drug Development Research, Journal Year: 2024, Volume and Issue: 86(1)

Published: Dec. 25, 2024

ABSTRACT The remarkable clinical success of third‐generation epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) has significantly advanced the treatment landscape for non‐small‐cell lung cancer (NSCLC). However, emergence tertiary point mutation C797S poses a substantial obstacle to their efficacy, leading dearth FDA‐approved targeted therapies patients harboring this mutation. Addressing pressing challenge necessitates development novel therapeutic agents targeting clinically challenging EGFR This review delves into design strategies, antitumor activity, and crucial protein–drug interactions recently introduced Orthoallosteric fourth‐generation EGFR‐TKIs. These are distinguished by ability simultaneously engage both canonical orthosteric (ATP) binding site allosteric site. By shedding light on these key aspects, serves as valuable resource medicinal chemists, empowering them propel advancement inhibitors.

Language: Английский

Orthoallosteric EGFR‐TKIs: A New Paradigm in NSCLC Treatment Strategy Targeting the C797S Mutation DOI Open Access
Iqrar Ahmad, Harun Patel

Drug Development Research, Journal Year: 2024, Volume and Issue: 86(1)

Published: Dec. 25, 2024

ABSTRACT The remarkable clinical success of third‐generation epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) has significantly advanced the treatment landscape for non‐small‐cell lung cancer (NSCLC). However, emergence tertiary point mutation C797S poses a substantial obstacle to their efficacy, leading dearth FDA‐approved targeted therapies patients harboring this mutation. Addressing pressing challenge necessitates development novel therapeutic agents targeting clinically challenging EGFR This review delves into design strategies, antitumor activity, and crucial protein–drug interactions recently introduced Orthoallosteric fourth‐generation EGFR‐TKIs. These are distinguished by ability simultaneously engage both canonical orthosteric (ATP) binding site allosteric site. By shedding light on these key aspects, serves as valuable resource medicinal chemists, empowering them propel advancement inhibitors.

Language: Английский

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