ArticleScience signaling2016
A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- Structural asymmetry in FGF23 signaling.Trends in pharmacological sciences · 2023Article
- Article
- Identification of Small-Molecule Inhibitors of Fibroblast Growth Factor 23 Signaling via In Silico Hot Spot Prediction and Molecular Docking to α-Klotho.Journal of chemical information and modeling · 2022Article
- Target-Based Small Molecule Drug Discovery for Colorectal Cancer: A Review of Molecular Pathways and In Silico Studies.Biomolecules · 2022Review
- The Saga of Endocrine FGFs.Cells · 2021Review
- Novel Small Molecule Fibroblast Growth Factor 23 Inhibitors Increase Serum Phosphate and Improve Skeletal Abnormalities inMolecular pharmacology · 2021Article
- Design and development of FGF-23 antagonists: Definition of the pharmacophore and initial structure-activity relationships probed by synthetic analogues.Bioorganic & medicinal chemistry · 2021Article
- Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.Journal of chemical information and modeling · 2020Article
- Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.ChemRxiv : the preprint server for chemistry · 2020Article
- Osteocytic FGF23 and Its Kidney Function.Frontiers in endocrinology · 2020Review
- Article
- Molecular Control of Phosphorus Homeostasis and Precision Treatment of Hypophosphatemic Disorders.Current molecular biology reports · 2019Article
- Fibroblast growth factor 23 and α-Klotho co-dependent and independent functions.Current opinion in nephrology and hypertension · 2019Review
- Ensemble Docking in Drug Discovery.Biophysical journal · 2018Review
- Ensemble docking to difficult targets in early-stage drug discovery: Methodology and application to fibroblast growth factor 23.Chemical biology & drug design · 2018Article
- Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis.The Journal of clinical investigation · 2018Article
- Role of Fibroblast Growth Factor-23 in Innate Immune Responses.Frontiers in endocrinology · 2018Review
- Targeting Fibroblast Growth Factor 23 Signaling with Antibodies and Inhibitors, Is There a Rationale?Frontiers in endocrinology · 2018Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Fibroblast growth factor-23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. Using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23-induced activation of the FGFR/α-KL complex. Additional modeling and functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL-dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. These chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.
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Identifiers
What OpenQuestion holds
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.