ArticleJournal of molecular biology2014
Structural mechanisms determining inhibition of the collagen receptor DDR1 by selective and multi-targeted type II kinase inhibitors.
Article in Journal of molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 96 citations in OpenAlex.
- Safety, tolerability, and pharmacokinetics of single and multiple topical ophthalmic administration of imatinib mesylate in healthy subjects.Clinical and translational science · 2022Trial
- Quantification of Binding of Small Molecules to Native Kinases by Flow Cytometry Reveals Divergence from Biochemical Affinities.Journal of the American Chemical Society · 2026Article
- Bioinformatic pipeline to identify potential therapeutic targets with subsequent isolation and characterization of novel human anti- DDR1 antibodies.Scientific reports · 2026Article
- ComTarget: Small-Molecule Target Prediction with Combinatorial Modeling.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Explanatory review on DDR inhibitors: their biological activity, synthetic route, and structure-activity relationship.Molecular diversity · 2025Review
- Structural basis for MEKK2 dimerization and substrate recognition.Nature communications · 2025Article
- Collagen type IV alpha 6 promotes tumor progression and chemoresistance in ovarian cancer by activating the discoidin domain receptor 1 pathway.Oncogenesis · 2025Article
- Estimation of Absolute Binding Free Energies for Drugs That Bind Multiple Proteins.Journal of chemical information and modeling · 2025Article
- Discovery of Novel DDR1 Inhibitors through a Hybrid Virtual Screening Pipeline, Biological Evaluation and Molecular Dynamics Simulations.ACS medicinal chemistry letters · 2025Article
- Drug discovery and mechanism prediction with explainable graph neural networks.Scientific reports · 2025Article
- Mothra: MultiobjectiveJournal of chemical information and modeling · 2024Article
- Virtual screening for potential discoidin domain receptor 1 (DDR1) inhibitors based on structural assessment.Molecular diversity · 2023Article
- DDR1 and Its Ligand, Collagen IV, Are Involved in In Vitro Oligodendrocyte Maturation.International journal of molecular sciences · 2023Article
- Focusing on discoidin domain receptors in premalignant and malignant liver diseases.Frontiers in oncology · 2023Review
- Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment.International journal of molecular sciences · 2022Review
- Article
- Identification of Synergistic Drug Combinations to Target KRAS-Driven Chemoradioresistant Cancers Utilizing Tumoroid Models of Colorectal Adenocarcinoma and Recurrent Glioblastoma.Frontiers in oncology · 2022Article
- Discoidin Domain Receptor 1, a Potential Biomarker and Therapeutic Target in Hepatocellular Carcinoma.International journal of general medicine · 2022Review
- Evolution of Functional Diversity in the Holozoan Tyrosine Kinome.Molecular biology and evolution · 2021Article
- The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The discoidin domain receptors (DDRs), DDR1 and DDR2, form a unique subfamily of receptor tyrosine kinases that are activated by the binding of triple-helical collagen. Excessive signaling by DDR1 and DDR2 has been linked to the progression of various human diseases, including fibrosis, atherosclerosis and cancer. We report the inhibition of these unusual receptor tyrosine kinases by the multi-targeted cancer drugs imatinib and ponatinib, as well as the selective type II inhibitor DDR1-IN-1. Ponatinib is identified as the more potent molecule, which inhibits DDR1 and DDR2 with an IC50 of 9nM. Co-crystal structures of human DDR1 reveal a DFG-out conformation (DFG, Asp-Phe-Gly) of the kinase domain that is stabilized by an unusual salt bridge between the activation loop and αD helix. Differences to Abelson kinase (ABL) are observed in the DDR1 P-loop, where a β-hairpin replaces the cage-like structure of ABL. P-loop residues in DDR1 that confer drug resistance in ABL are therefore accommodated outside the ATP pocket. Whereas imatinib and ponatinib bind potently to both the DDR and ABL kinases, the hydrophobic interactions of the ABL P-loop appear poorly satisfied by DDR1-IN-1 suggesting a structural basis for its DDR1 selectivity. Such inhibitors may have applications in clinical indications of DDR1 and DDR2 overexpression or mutation, including lung cancer.
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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.