ArticleACS medicinal chemistry letters2015
Fragment-Based Discovery of Potent and Selective DDR1/2 Inhibitors.
Article in ACS medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 61 citations in OpenAlex.
- Article
- Collagen in Fibrotic Diseases.Sub-cellular biochemistry · 2026Review
- Carboxamide: A Privileged Pharmacophore for the Development of Anti-infectious and Anti-cancer Drugs.Current topics in medicinal chemistry · 2026Review
- Explanatory review on DDR inhibitors: their biological activity, synthetic route, and structure-activity relationship.Molecular diversity · 2025Review
- Token-Mol 1.0: tokenized drug design with large language models.Nature communications · 2025Article
- A small bowel adenocarcinoma harboring a DDR2 mutation in a celiac patient.Clinical journal of gastroenterology · 2024Article
- Identification of Ureidocoumarin-Based Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors via Drug Repurposing Approach, Biological Evaluation, and In Silico Studies.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Design, Synthesis, and Evaluation of New 1Journal of medicinal chemistry · 2024Article
- Virtual screening for potential discoidin domain receptor 1 (DDR1) inhibitors based on structural assessment.Molecular diversity · 2023Article
- Review
- Discovery of 4-cyclopropyl-3-(2-((1-cyclopropyl-1Acta pharmaceutica Sinica. B · 2022Article
- Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation.Biomolecules · 2021Review
- C-H functionalisation tolerant to polar groups could transform fragment-based drug discovery (FBDD).Chemical science · 2021Article
- Expression and subcellular localization of Discoidin Domain Receptor 1 (DDR1) define prostate cancer aggressiveness.Cancer cell international · 2021Article
- The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer.International journal of molecular sciences · 2021Review
- Dasatinib-SIK2 Binding Elucidated by Homology Modeling, Molecular Docking, and Dynamics Simulations.ACS omega · 2021Article
- Two-step release of kinase autoinhibition in discoidin domain receptor 1.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Design and Optimization of 3'-(Imidazo[1,2-ACS medicinal chemistry letters · 2020Article
- Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease.Frontiers in aging neuroscience · 2020Review
- What Makes a Kinase Promiscuous for Inhibitors?Cell chemical biology · 2019Article
Corrections and comments
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The DDR1 and DDR2 receptor tyrosine kinases are activated by extracellular collagen and have been implicated in a number of human diseases including cancer. We performed a fragment-based screen against DDR1 and identified fragments that bound either at the hinge or in the back pocket associated with the DFG-out conformation of the kinase. Modeling based on crystal structures of potent kinase inhibitors facilitated the "back-to-front" design of potent DDR1/2 inhibitors that incorporated one of the DFG-out fragments. Further optimization led to low nanomolar, orally bioavailable inhibitors that were selective for DDR1 and DDR2. The inhibitors were shown to potently inhibit DDR2 activity in cells but in contrast to unselective inhibitors such as dasatinib, they did not inhibit proliferation of mutant DDR2 lung SCC cell lines.
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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.