ArticleJournal of medicinal chemistry2014
Design, synthesis, and evaluation of nonretinoid retinol binding protein 4 antagonists for the potential treatment of atrophic age-related macular degeneration and Stargardt disease.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 51 citations in OpenAlex.
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- The baseline vitreous proteome in rhegmatogenous retinal detachment: a case-control study of proliferative vitreoretinopathy.Scientific reports · 2026Article
- The Liver-Eye Axis of Dietary Vitamin A Homeostasis: A Review of Mechanisms, Receptors, and Visual Outcomes.Nutrients · 2026Review
- Retinoid dynamics in vision: from visual cycle biology to retina disease treatments.Pharmacology & therapeutics · 2025Review
- Investigation of a squaramide motif as a bioisostere of the amino-acid group of S-adenosyl-L-methionine and its functional impact on RNA methylation.Communications chemistry · 2025Article
- Highly stereoselective synthesis of polysubstituted housanes and spiro-oxa-housanes: application and mechanistic insights.Chemical science · 2025Article
- Advances and therapeutic opportunities in visual cycle modulation.Progress in retinal and eye research · 2025Review
- Retinoids and retinoid-binding proteins: Unexpected roles in metabolic disease.Current topics in developmental biology · 2025Review
- Oxidative Stress, Persistent Inflammation and Blood Coagulation Alterations in Serum Proteome of Patients with Neovascular Age-Related Macular Degeneration.Life (Basel, Switzerland) · 2024Article
- Targeting Retinol-Binding Protein 4 (RBP4) in the Management of Cardiometabolic Diseases.Cardiovascular toxicology · 2023Review
- Analysis of Retinol Binding Protein 4 andDiagnostics (Basel, Switzerland) · 2023Article
- Article
- Recent Advances in Age-Related Macular Degeneration Therapies.Molecules (Basel, Switzerland) · 2022Review
- Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease.Nutrients · 2022Review
- Synthesis, Structure, and Antiproliferative Action of 2-Pyridyl Urea-Based Cu(II) Complexes.Biomedicines · 2022Article
- Administration of Melatonin in Diabetic Retinopathy Is Effective and Improves the Efficacy of Mesenchymal Stem Cell Treatment.Stem cells international · 2022Article
- Identification of Transthyretin Tetramer Kinetic Stabilizers That Are Capable of Inhibiting the Retinol-Dependent Retinol Binding Protein 4-Transthyretin Interaction: Potential Novel Therapeutics for Macular Degeneration, Transthyretin Amyloidosis, and Their Common Age-Related Comorbidities.Journal of medicinal chemistry · 2021Article
- Biological Functions of RBP4 and Its Relevance for Human Diseases.Frontiers in physiology · 2021Review
- Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities.Journal of medicinal chemistry · 2020Article
- Comparative pharmacokinetics and pharmacodynamics of the advanced Retinol-Binding Protein 4 antagonist in dog and cynomolgus monkey.PloS one · 2020Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4(-/-) mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%.
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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.