ArticleJournal of medicinal chemistry2015
Bicyclic [3.3.0]-Octahydrocyclopenta[c]pyrrolo Antagonists of Retinol Binding Protein 4: Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 32 citations in OpenAlex.
- Intracellular Retinoid-Binding Proteins (CRBP, CRALBP, CRABP) as Emerging Drug Targets in Retinal Disease.International journal of molecular sciences · 2026Review
- The Liver-Eye Axis of Dietary Vitamin A Homeostasis: A Review of Mechanisms, Receptors, and Visual Outcomes.Nutrients · 2026Review
- Retinol-binding protein 4 in cardiovascular diseases: mechanisms and therapeutic perspectives.Frontiers in cardiovascular medicine · 2026Review
- Mechanisms and Functions of Chromophore Regeneration in the Classical Visual Cycle: Implications for Retinal Disease Pathogenesis and Therapy.Biomolecules · 2025Review
- Advances and therapeutic opportunities in visual cycle modulation.Progress in retinal and eye research · 2025Review
- Oxidative Stress, Persistent Inflammation and Blood Coagulation Alterations in Serum Proteome of Patients with Neovascular Age-Related Macular Degeneration.Life (Basel, Switzerland) · 2024Article
- Discovery of Nonretinoid Inhibitors of CRBP1: Structural and Dynamic Insights for Ligand-Binding Mechanisms.ACS chemical biology · 2023Article
- Recent Advances in Age-Related Macular Degeneration Therapies.Molecules (Basel, Switzerland) · 2022Review
- 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
- Novel Possible Protein Targets in Neovascular Age-Related Macular Degeneration: A Pilot Study Experiment.Frontiers in medicine · 2021Article
- 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
- Design, Synthesis, and Preclinical Efficacy of Novel Nonretinoid Antagonists of Retinol-Binding Protein 4 in the Mouse Model of Hepatic Steatosis.Journal of medicinal chemistry · 2019Article
- A non-retinoid antagonist of retinol-binding protein 4 rescues phenotype in a model of Stargardt disease without inhibiting the visual cycle.The Journal of biological chemistry · 2018Article
- Vitreous levels of apolipoprotein A1 and retinol binding protein 4 in human rhegmatogenous retinal detachment associated with choroidal detachment.Molecular vision · 2018Article
- Drugs for rare disorders.British journal of clinical pharmacology · 2017Article
- Computer-aided drug discovery research at a global contract research organization.Journal of computer-aided molecular design · 2017Article
- Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Dry Age-Related Macular Degeneration Pharmacology.Handbook of experimental pharmacologyArticle
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Antagonists of retinol-binding protein 4 (RBP4) impede ocular uptake of serum all-trans retinol (1) and have been shown to reduce cytotoxic bisretinoid formation in the retinal pigment epithelium (RPE), which is associated with the pathogenesis of both dry age-related macular degeneration (AMD) and Stargardt disease. Thus, these agents show promise as a potential pharmacotherapy by which to stem further neurodegeneration and concomitant vision loss associated with geographic atrophy of the macula. We previously disclosed the discovery of a novel series of nonretinoid RBP4 antagonists, represented by bicyclic [3.3.0]-octahydrocyclopenta[c]pyrrolo analogue 4. We describe herein the utilization of a pyrimidine-4-carboxylic acid fragment as a suitable isostere for the anthranilic acid appendage of 4, which led to the discovery of standout antagonist 33. Analogue 33 possesses exquisite in vitro RBP4 binding affinity and favorable drug-like characteristics and was found to reduce circulating plasma RBP4 levels in vivo in a robust manner (>90%).
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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.