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Article

Discovery of the First Highly Selective and Broadly Effective Macrocycle-Based Type II TRK Inhibitors that Overcome Clinically Acquired Resistance.

Journal of medicinal chemistry - 28 Apr 2022

Wang Zuqin, Wang Jie, Wang Yongjin, Xiang Shuang, Song Xiaojuan, Tu Zhengchao, Zhou Yang, Zhang Zhi-Min, Zhang Zhang, Ding Ke, Lu Xiaoyun

Abstract excerpt

Tropomyosin receptor kinase (TRK) secondary mutations mediating acquired resistance, especially at the solvent-front (SF) and the DFG motif, represent an unmet clinical need. Small-molecule macrocyclic kinase inhibitors have displayed significant advantages in overcoming clinical resistance driven by kinase mutations; however, all reported small-molecule macrocyclic TRK inhibitors are all type I inhibitors and...

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Identifiers

PMID: 35426680
DOI: 10.1021/acs.jmedchem.2c00308

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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Discovery of the First Highly Selective and Broadly Effective Macrocycle-Based Type II TRK Inhibitors that Overcome Clinically Acquired Resistance.PMID 35426680Read ↗

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