ArticleACS medicinal chemistry letters2019
Structural and Molecular Insight into Resistance Mechanisms of First Generation cMET Inhibitors.
Article in ACS medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed.
- Medicinal Chemistry of Small-Molecule c-Met Inhibitors: From Approved Therapies to Emerging Multitarget Anticancer Agents.International journal of molecular sciences · 2026Review
- Molecular Basis of c‑MET Inhibition by Approved Small Molecule Drugs: A Structural Perspective.ACS medicinal chemistry letters · 2026Review
- Tyrosine-Mediated Static and Dynamic Quenching of a Receptor Tyrosine Kinase Biosensor Reveals Inhibitor Binding Modes and Kinase Conformations.ACS chemical biology · 2025Article
- Molecular mechanism of type ib MET inhibitors and their potential for CNS tumors.Scientific reports · 2025Article
- Characterization of Bozitinib as a potential therapeutic agent for MET-amplified gastric cancer.Communications biology · 2025Article
- Pharmacophoric analogs of Savolitinib reveal promising inhibitors of the c-MET receptor tyrosine kinase for drug discovery: in silico investigation.In silico pharmacology · 2025Article
- Design and Synthesis of c-Met and HDAC Dual Inhibitors for the Treatment of Breast Cancer.ACS medicinal chemistry letters · 2024Article
- MET exon 14 skipping mutation drives cancer progression and recurrence via activation of SMAD2 signalling.British journal of cancer · 2024Article
- Screening Ultra-Large Encoded Compound Libraries Leads to Novel Protein-Ligand Interactions and High Selectivity.Journal of medicinal chemistry · 2024Review
- Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer.Science advances · 2023Article
- Discovery and Optimization of the First ATP Competitive Type-III c-MET Inhibitor.Journal of medicinal chemistry · 2023Article
- The Importance of the Pyrazole Scaffold in the Design of Protein Kinases Inhibitors as Targeted Anticancer Therapies.Molecules (Basel, Switzerland) · 2023Review
- The Preclinical Pharmacology of Tepotinib-A Highly Selective MET Inhibitor with Activity in Tumors Harboring MET Alterations.Molecular cancer therapeutics · 2023Review
- Structural insight into the macrocyclic inhibitor TPX-0022 of c-Met and c-Src.Computational and structural biotechnology journal · 2023Article
- Foretinib can overcome common on-target resistance mutations after capmatinib/tepotinib treatment in NSCLCs with MET exon 14 skipping mutation.Journal of hematology & oncology · 2022Article
- Artonin F Induces the Ubiquitin-Proteasomal Degradation of c-Met and Decreases Akt-mTOR Signaling.Pharmaceuticals (Basel, Switzerland) · 2022Article
- MET Exon 14 Splice-Site Mutations Preferentially Activate KRAS Signaling to Drive Tumourigenesis.Cancers · 2022Article
- Review
- Chemistry, Biosynthesis, Physicochemical and Biological Properties of Rubiadin: A Promising Natural Anthraquinone for New Drug Discovery and Development.Drug design, development and therapy · 2021Review
- SHP2 Inhibition Influences Therapeutic Response to Tepotinib in Tumors with MET Alterations.iScience · 2020Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many small molecule inhibitors of the cMET receptor tyrosine kinase have been evaluated in clinical trials for the treatment of cancer and resistance-conferring mutations of cMET are beginning to be reported for a number of such compounds. There is now a need to understand specific cMET mutations at the molecular level, particularly concerning small molecule recognition. Toward this end, we report here the first crystal structures of the recent clinically observed resistance-conferring D1228V cMET mutant in complex with small molecule inhibitors, along with a crystal structure of wild-type cMET bound by the clinical compound savolitinib and supporting cellular, biochemical, and biophysical data. Our findings indicate that the D1228V alteration induces conformational changes in the kinase, which could have implications for small molecule inhibitor design. The data we report here increases our molecular understanding of the D1228V cMET mutation and provides insight for future inhibitor design.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.