ArticleMolecular pharmacology2015
Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 23 citations in OpenAlex.
- Retinoid dynamics in vision: from visual cycle biology to retina disease treatments.Pharmacology & therapeutics · 2025Review
- Advances and therapeutic opportunities in visual cycle modulation.Progress in retinal and eye research · 2025Review
- Tuning the Metabolic Stability of Visual Cycle Modulators through Modification of an RPE65 Recognition Motif.Journal of medicinal chemistry · 2023Article
- From mouse to human: Accessing the biochemistry of vision in vivo by two-photon excitation.Progress in retinal and eye research · 2023Review
- Peptide Derivatives of Retinylamine Prevent Retinal Degeneration with Minimal Side Effects on Vision in Mice.Bioconjugate chemistry · 2021Article
- The molecular aspects of absorption and metabolism of carotenoids and retinoids in vertebrates.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Development of chiral fluorinated alkyl derivatives of emixustat as drug candidates for the treatment of retinal degenerative diseases.Bioorganic & medicinal chemistry letters · 2020Article
- Impacts of deletion and ichthyosis prematurity syndrome-associated mutations in fatty acid transport protein 4 on the function of RPE65.FEBS letters · 2020Article
- New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Retinoid isomerase inhibitors impair but do not block mammalian cone photoreceptor function.The Journal of general physiology · 2018Article
- Allosteric modulation of the substrate specificity of acyl-CoA wax alcohol acyltransferase 2.Journal of lipid research · 2017Article
- Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures.The Journal of biological chemistry · 2016Article
- Retinylamine Benefits Early Diabetic Retinopathy in Mice.The Journal of biological chemistry · 2015Article
- Molecular pharmacodynamics of emixustat in protection against retinal degeneration.The Journal of clinical investigation · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation.
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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.