Discover Community Create You

Loading publication...

Noodle always counts identifier-free feature events for service operation. With your permission, Google Analytics can also estimate audience and engagement. Search text, publication identifiers, cookies, IP addresses and browser fingerprints are never included in Noodle's first-party event counters.

Privacy details

Article

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

Bioorganic chemistry - 15 Jul 2025

Zhao Wei, Wang Zhenghai, Chen Yinbo, Zhao Weiwei, Xie Zhendong, Chu Yong, Zhu Xueyan, Zhang Peng

Abstract excerpt

Tropomyosin receptor kinases (TRKs), a superfamily of transmembrane receptor tyrosine kinases, have recently attracted extensive attention as promising cancer therapeutic targets since the FDA approval of Larotrectinib and Entrectinib. However, the emergence of acquired resistance due to secondary mutations in the TRKs domain significantly diminshes the therapeutic efficacy of these drugs, highlighting an urgent...

Read the complete abstract on PubMed

Topics

Share this publication in a Topic to start or enrich a Post.

Share to Drug Discovery
Share to Drug Resistance, Neoplasm

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Share to Drug Screening Assays, Antitumor

Share to Molecular Structure

Share to Protein Kinase Inhibitors

Share to Receptor, trkA

Share to Structure-Activity Relationship

Source

Identifiers

PMID: 40398186
DOI: 10.1016/j.bioorg.2025.108590

Genes

LMNA

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026.

Related research

Semantic proximity does not establish scientific evidence.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

Discovery of novel diarylurea derivatives as potent type II TRK inhibitors for combating multiple acquired resistant mutants.PMID 40398186Read ↗

Discovery of imidazo[1,2-b]pyridazine derivatives as potent TRK inhibitors for overcoming multiple resistant mutants.Semantic proximity Read ↗

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

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

Switch type I to type II TRK inhibitors for combating clinical resistance induced by xDFG mutation for cancer therapy.Semantic proximity Read ↗

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

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

Discovery of (E)-N-(4-methyl-5-(3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thiazol-2-yl)-2-(4-methylpiperazin-1-yl)acetamide (IHMT-TRK-284) as a novel orally available type II TRK kinase inhibitor capable of overcoming multiple resistant mutants.Semantic proximity Read ↗

Development of PROTACs for targeted degradation of oncogenic TRK fusionsSemantic proximity Read ↗

Targeting TRK: A Fast Tracked Application of Precision Oncology and Future DirectionsSemantic proximity Read ↗

TRK inhibitor activity and resistance in TRK fusion-positive cancers in adults.Semantic proximity Read ↗

⌁Select a neighboring publication to make it the new centre.