ArticleBioorganic & medicinal chemistry2016
Sobetirome prodrug esters with enhanced blood-brain barrier permeability.
Article in Bioorganic & medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Ester Prodrug NLRP3 Inflammasome Inhibitor NT-0796 is Brain Active due to Activation by Local Expression of Carboxylesterase-1.ACS chemical neuroscience · 2026Article
- MolGraph-xLSTM as a graph-based dual-level xLSTM framework for enhanced molecular representation and interpretability.Communications chemistry · 2025Article
- Interference with systemic negative feedback as a potential mechanism for nonmonotonic dose-responses of endocrine-disrupting chemicals.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Drug discovery targeting thyroid hormone receptorActa pharmaceutica Sinica. B · 2025Review
- Synthesis and preclinical testing of a selective beta-subtype agonist of thyroid hormone receptor ZTA-261.Communications medicine · 2024Article
- Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt-Hopkins syndrome.Brain : a journal of neurology · 2023Article
- Maternal Administration of the CNS-Selective Sobetirome Prodrug Sob-AM2 Exerts Thyromimetic Effects in Murine MCT8-Deficient Fetuses.Thyroid : official journal of the American Thyroid Association · 2023Article
- Influence of hormones in multiple sclerosis: focus on the most important hormones.Metabolic brain disease · 2023Review
- TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor.Cell chemical biology · 2022Article
- Inulin and Its Application in Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2021Review
- From Combinations to Single-Molecule Polypharmacology-Cromolyn-Ibuprofen Conjugates for Alzheimer's Disease.Molecules (Basel, Switzerland) · 2021Article
- Microemulsion-Based Media in Nose-to-Brain Drug Delivery.Pharmaceutics · 2021Review
- Overcoming the blood-brain barrier in neurodegenerative disorders and brain tumours.IET nanobiotechnology · 2020Review
- Thyroid Hormone Analogues: An Update.Thyroid : official journal of the American Thyroid Association · 2020Review
- Pharmacological Complementation Remedies an Inborn Error of Lipid Metabolism.Cell chemical biology · 2020Article
- Selective Thyroid Hormone Receptor-Beta (TRβ) Agonists: New Perspectives for the Treatment of Metabolic and Neurodegenerative Disorders.Frontiers in medicine · 2020Review
- Myelin repair stimulated by CNS-selective thyroid hormone action.JCI insight · 2019Article
- Machine Learning Approach for Determining the Formation of β-Lactam Antibiotic Complexes with Cyclodextrins Using Multispectral Analysis.Molecules (Basel, Switzerland) · 2019Article
- Structure-Activity Relationships of Central Nervous System Penetration by Fatty Acid Amide Hydrolase (FAAH)-Targeted Thyromimetic Prodrugs.ACS medicinal chemistry letters · 2019Article
- Sobetirome and its Amide Prodrug Sob-AM2 Exert Thyromimetic Actions in Mct8-Deficient Brain.Thyroid : official journal of the American Thyroid Association · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
There is currently great interest in developing drugs that stimulate myelin repair for use in demyelinating diseases such as multiple sclerosis. Thyroid hormone plays a key role in stimulating myelination during development and also controls the expression of important genes involved in myelin repair in adults. Because endogenous thyroid hormone in excess lacks a generally useful therapeutic index, it is not used clinically for indications other than hormone replacement; however, selective thyromimetics such as sobetirome offer a therapeutic alternative. Sobetirome is the only clinical-stage thyromimetic that is known to cross the blood-brain-barrier (BBB) and we endeavored to increase the BBB permeability of sobetirome using a prodrug strategy. Ester prodrugs of sobetirome were prepared based on literature reports of improved BBB permeability with other carboxylic acid containing drugs and BBB permeability was assessed in vivo. One sobetirome prodrug, ethanolamine ester 11, was found to distribute more sobetirome to the brain compared to an equimolar peripheral dose of unmodified sobetirome. In addition to enhanced brain levels, prodrug 11 displayed lower sobetirome blood levels and a brain/serum ratio that was larger than that of unmodified sobetirome. Thus, these data indicate that an ester prodrug strategy applied to sobetirome can deliver increased concentrations of the active drug to the central nervous system (CNS), which may prove useful in the treatment of CNS disorders.
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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.