ArticleNature communications2024
Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 22 citations in OpenAlex.
- Myelin Dynamics at the Axon-Oligodendrocyte Interface: Adaptive Conduction Homeostasis in Demyelination, Remyelination and White Matter Repair.International journal of molecular sciences · 2026Review
- Structure-based scaffold hopping reveals strategies to overcome oncogenic KIT and PDGFRA mutation-driven drug-resistance in GIST.Nature communications · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Molecular Mechanisms of KIT Receptor Dimerization and Oncogenic Activation Revealed by Multiscale Simulations.Journal of chemical information and modeling · 2026Article
- Article
- Predicting Clinical Sensitivities of PDGFRA Exon 18 Mutations to Imatinib and Avapritinib to Optimize Gastrointestinal Stromal Tumor Treatment.Cancer research communications · 2026Article
- Combinatorial Targeting of Avapritinib-Driven MAP Kinase Activation in High-Grade Glioma.Research square · 2026Article
- Sustainable high-throughput microwell spectrophotometric methods for avapritinib quality control via charge-transfer complexation.Scientific reports · 2026Article
- Selective Inhibition of VEGFR2 in Preference to Other Receptor Tyrosine Kinases by Diosgenin, a Natural Steroidal Sapogenin.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Pyrazolylpyrimidinamines Decorated via Petasis Reaction as Small-Molecule Activators of the RNA-Degrading Ribonuclease IRE1α.ACS bio & med chem Au · 2026Article
- Metadynamics reveals luteolin-mediated conformational stabilization against avapritinib-resistant PDGFRα D842V/G680R GIST.Scientific reports · 2026Article
- The Evolving Role of Second- and Third-Generation Tyrosine Kinase Inhibitors in Gastrointestinal Malignancies: Advances in Targeted Therapy with Sunitinib, Regorafenib, and Avapritinib.Journal of clinical medicine · 2026Review
- The Mechanisms of Imatinib Resistance in Gastrointestinal Stromal Tumours: Theoretical Basis and Therapeutic Aspect.Journal of cellular and molecular medicine · 2025Review
- Clinical and preclinical insights into a novel MDM2::PDGFRA fusion in recurrent glioblastoma.NPJ precision oncology · 2025Article
- Absolute Configuration and Chiroptical Properties of Flexible Drug Avapritinib.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Targeted inhibition of PDGFRA with avapritinib, markedly enhances lenvatinib efficacy in hepatocellular carcinoma in vitro and in vivo: clinical implications.Journal of experimental & clinical cancer research : CR · 2025Article
- Interaction of Avapritinib with Congo Red in Pancreatic Cancer Cells: Molecular Modeling and Biophysical Studies.International journal of molecular sciences · 2025Article
- Gene Mutations in Gastrointestinal Stromal Tumors: Advances in Treatment and Mechanism Research.Global medical genetics · 2024Review
- Review
- Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review.Experimental hematology & oncology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Avapritinib is the only potent and selective inhibitor approved for the treatment of D842V-mutant gastrointestinal stromal tumors (GIST), the most common primary mutation of the platelet-derived growth factor receptor α (PDGFRA). The approval was based on the NAVIGATOR trial, which revealed overall response rates of more than 90%. Despite this transformational activity, patients eventually progress, mostly due to acquired resistance mutations or following discontinuation due to neuro-cognitive side effects. These patients have no therapeutic alternative and face a dismal prognosis. Notable, little is known about this drug's binding mode and its medicinal chemistry development, which is instrumental for the development of the next generation of drugs. Against this background, we solve the crystal structures of avapritinib in complex with wild-type and mutant PDGFRA and stem cell factor receptor (KIT), which provide evidence and understanding of inhibitor binding and lead to the identification of a sub-pocket (Gα-pocket). We utilize this information to design, synthesize and characterize avapritinib derivatives for the determination of key pharmacophoric features to overcome drug resistance and limit potential blood-brain barrier penetration.
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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.