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Article

Discovery of Next-Generation Tropomyosin Receptor Kinase Inhibitors for Combating Multiple Resistance Associated with Protein Mutation.

Journal of medicinal chemistry - 28 Oct 2021

Zhuo Lin-Sheng, Wang Ming-Shu, Wu Feng-Xu, Xu Hong-Chuang, Gong Yi, Yu Zhi-Cheng, Tian Yan-Guang, Pang Chao, Hao Ge-Fei, Huang Wei, Yang Guang-Fu

Abstract excerpt

Tropomyosin receptor kinase (TRK) inhibition is an effective therapeutic approach for treatment of a variety of cancers. Despite the use of first-generation TRK inhibitor (TRKI) larotrectinib (1) resulting in significant therapeutic response in patients, acquired resistance develops invariably. The emergence of secondary mutations occurring at the solvent-front, xDFG, and gatekeeper regions of TRK represents a...

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Identifiers

PMID: 34668694
DOI: 10.1021/acs.jmedchem.1c01539

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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 Next-Generation Tropomyosin Receptor Kinase Inhibitors for Combating Multiple Resistance Associated with Protein Mutation.PMID 34668694Read ↗

Discovery of Next-Generation Tropomyosin Receptor Kinase (TRK) Inhibitors for Combatting Resistance Associated with Protein MutationSemantic proximity Read ↗

Structure-Based Optimization of the Third Generation Type II Macrocycle TRK Inhibitors with Improved Activity against Solvent-Front, xDFG, and Gatekeeper Mutations.Semantic proximity Read ↗

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Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinibSemantic proximity Read ↗

Discovery of novel diarylurea derivatives as potent type II TRK inhibitors for combating multiple acquired resistant mutants.Semantic proximity Read ↗

JND4135, a New Type II TRK Inhibitor, Overcomes TRK xDFG and Other Mutation Resistance In Vitro and In Vivo.Semantic proximity Read ↗

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