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Article

Discovery of Highly Selective AKR1C3 Inhibitors to Overcome EGFR C797S-Mediated Osimertinib Resistance in Non-Small Cell Lung Cancer.

Journal of medicinal chemistry - 26 Mar 2026

Guo Can, Wang Xiaolong, Guan Qianwen, Zhong Sheng, Zhang Lu, Liu Yimeng, Han Bingjie, Shao Jikuan, Liu Zongliang, Chen Yao, Sun Haopeng

Abstract excerpt

Osimertinib resistance driven by the cis-C797S/T790M EGFR triplet mutation remains clinically intractable. We identify aldo-keto reductase 1C3 (AKR1C3) as a metabolic vulnerability that sustains glutathione-reactive oxygen species (GSH-ROS) homeostasis in resistant non-small cell lung cancer (NSCLC). Starting from the selective inhibitor S07-2001, six rounds of structure-guided optimization delivered 55...

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Source

Identifiers

PMID: 41612551
DOI: 10.1021/acs.jmedchem.5c03655

Genes

AKR1C3
EGFR
AKR1C1
AKR1C2
AKR1C4

Variants

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 8 Sept 2026.

Related research

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Discovery of Highly Selective AKR1C3 Inhibitors to Overcome EGFR C797S-Mediated Osimertinib Resistance in Non-Small Cell Lung Cancer.PMID 41612551Read ↗

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