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

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

Journal of medicinal chemistry - 28 Sept 2023

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

Abstract excerpt

The solvent-front (SF), gatekeeper, and xDFG motif mutations of tropomyosin receptor kinase (TRK) mediating acquired resistance of larotrectinib and entrectinib represent an unmet clinical need. To date, no effective drugs are being approved to overcome these mutants. Thus, a series of macrocycle compounds were designed and synthesized as new type II TRK inhibitors to combat clinically relevant mutations. The...

Read the complete abstract on PubMed

Topics

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

Share to Antineoplastic Agents
Share to Mutation

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Share to Neoplasms

Share to Protein Kinase Inhibitors

Share to Receptor, trkA

Source

Identifiers

PMID: 37676745
DOI: 10.1021/acs.jmedchem.3c00899

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 3 Sept 2026.

Related research

Semantic proximity does not establish scientific evidence.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

Structure-Based Optimization of the Third Generation Type II Macrocycle TRK Inhibitors with Improved Activity against Solvent-Front, xDFG, and Gatekeeper Mutations.PMID 37676745Read ↗

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

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

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

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

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

Exploring the kinase-inhibitor fragment interaction space facilitates the discovery of kinase inhibitor overcoming resistance by mutations.Semantic proximity Read ↗

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

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

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

Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations.Semantic proximity Read ↗

NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors.Semantic proximity Read ↗

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