ArticleACS chemical biology2019
DNA-Encoded Library-Derived DDR1 Inhibitor Prevents Fibrosis and Renal Function Loss in a Genetic Mouse Model of Alport Syndrome.
Article in ACS chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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
45 citing papers in PubMed, 110 citations in OpenAlex.
- Accelerated basement membrane remodeling and serum matrix fragments as biomarkers of fibrosis in Alport syndrome.Cell reports · 2026Article
- Treatment Approaches for Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2026Review
- Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine.Renal failure · 2025Review
- Explanatory review on DDR inhibitors: their biological activity, synthetic route, and structure-activity relationship.Molecular diversity · 2025Review
- af2rave: protein ensemble generation with physics-based sampling.Digital discovery · 2025Article
- Lipidomics Unveils Critical Lipid Pathway Shifts in Alport Syndrome.Kidney international reports · 2025Article
- Genotype-Based Molecular Mechanisms in Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2025Review
- From mundane to surprising nonadditivity: drivers and impact on ML models.Journal of computer-aided molecular design · 2024Article
- Optimization of a Novel DEL Hit That Binds in the Cbl-b SH2 Domain and Blocks Substrate Binding.ACS medicinal chemistry letters · 2024Article
- Impact of library input on the hit discovery rate in DNA-encoded chemical library selections.Chemical science · 2023Article
- Improving drug discovery with a hybrid deep generative model using reinforcement learning trained on a Bayesian docking approximation.Journal of computer-aided molecular design · 2023Article
- Virtual screening for potential discoidin domain receptor 1 (DDR1) inhibitors based on structural assessment.Molecular diversity · 2023Article
- Small-molecule discovery through DNA-encoded libraries.Nature reviews. Drug discovery · 2023Review
- Review
- Deep Learning Approach for the Discovery of Tumor-Targeting Small Organic Ligands from DNA-Encoded Chemical Libraries.ACS omega · 2023Article
- Machine-Learning-Based Data Analysis Method for Cell-Based Selection of DNA-Encoded Libraries.ACS omega · 2023Article
- Combining pharmacophore models derived from DNA-encoded chemical libraries with structure-based exploration to predict Tankyrase 1 inhibitors.European journal of medicinal chemistry · 2023Article
- Navigating chemical reaction space - application to DNA-encoded chemistry.Chemical science · 2022Article
- Discovery of 4-cyclopropyl-3-(2-((1-cyclopropyl-1Acta pharmaceutica Sinica. B · 2022Article
- Strategies for developing DNA-encoded libraries beyond binding assays.Nature chemistry · 2022Review
Corrections and comments
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Authors and funding
30 authors at 7 institutions in 3 countries.
Funding
Abstract
The importance of Discoidin Domain Receptor 1 (DDR1) in renal fibrosis has been shown via gene knockout and use of antisense oligonucleotides; however, these techniques act via a reduction of DDR1 protein, while we prove the therapeutic potential of inhibiting DDR1 phosphorylation with a small molecule. To date, efforts to generate a selective small-molecule to specifically modulate the activity of DDR1 in an in vivo model have been unsuccessful. We performed parallel DNA encoded library screens against DDR1 and DDR2, and discovered a chemical series that is highly selective for DDR1 over DDR2. Structure-guided optimization efforts yielded the potent DDR1 inhibitor 2.45, which possesses excellent kinome selectivity (including 64-fold selectivity over DDR2 in a biochemical assay), a clean in vitro safety profile, and favorable pharmacokinetic and physicochemical properties. As desired, compound 2.45 modulates DDR1 phosphorylation in vitro as well as prevents collagen-induced activation of renal epithelial cells expressing DDR1. Compound 2.45 preserves renal function and reduces tissue damage in Col4a3
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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.