Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The sphingosine-1-phosphate-1 (S1P) receptor agonists have great potential for the treatment of multiple sclerosis (MS) because they can inhibit lymphocyte egress through receptor internalization. We designed and synthesized triazole and isoxazoline derivatives to discover a novel S1P agonist for MS treatment. Of the two scaffolds, the isoxazoline derivative was determined to have excellent efficacy and drug-like properties. Among them, compound was found to have superior drug-like properties as well as excellent efficacies (EC = 7.03 nM in β-arrestin recruitment and EC = 11.8 nM in internalization). We also confirmed that effectively inhibited lymphocyte egress in the peripheral lymphocyte count test and significantly improved the clinical score in the experimental autoimmune encephalitis MS mouse model.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.1c01979 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modulation of T Cell Regulation by Interleukin-2 Agonists: Mechanisms and Clinical Implications.
Crit Rev Immunol
January 2025
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Dist. Medchal,500078, Telangana State, India.
IL-2 agonists significantly modulate T cell regulation, impacting activation, proliferation, differentiation, and immune homeostasis. Interleukin-2 (IL-2) is crucial for T cell growth and function, binding to the IL-2 receptor to trigger signaling pathways that balance immune responses. IL-2 promotes the expansion of effector T cells and enhances regulatory T cells (Tregs), preventing autoimmune responses.
View Article and Find Full Text PDFSREBP-mediated Signaling Restores Stem Cell Niche Properties in Human Lung Fibroblasts.
Am J Respir Cell Mol Biol
September 2025
INSERM U955 , Département de Physiologie, Hôpital Henri Mondor, AP-HP, DHU A-TVB France, Creteil, France;
Emphysema is characterized by chronic alveolar destruction. Lipofibroblasts (LIF) are crucial in the stem cell niche surrounding alveolar type II (AT2) cells and may contribute to alveolar regeneration. We aim to determine whether emphysema is associated with LIF reduction and whether Sterol regulatory binding protein (SREBP) activation promotes LIF differentiation and fibroblast stem cell niche properties.
View Article and Find Full Text PDF[New therapeutic approaches for the treatment of primary biliary cholangitis].
Med Sci (Paris)
September 2025
Service des maladies de l'appareil digestif. Centre de compétence Maladies rares « Maladies inflammatoires des voies biliaires et hépatites autoimmunes », Hôpital Huriez, Lille, France.
Primary biliary cholangitis (PBC) is a rare disease for which management long consisted of a single treatment: ursodeoxycholic acid. In 2015-2016, this disease regained interest with the first studies on obeticholic acid (FXR agonist) and then on bezafibrate (PPAR agonist). Subsequently, over the past five years, significant progress has been made in the management of PBC.
View Article and Find Full Text PDFThe effect of exogenous melatonin and melatonin receptor agonists on intensive care unit and hospital length of stay: A systematic review and meta-analysis.
PLoS One
September 2025
Catherine McAuley School of Nursing and Midwifery, University College Cork, Cork, Ireland.
Introduction: Melatonin supplements and melatonin receptor agonists are linked to reduced delirium in the Intensive Care Unit (ICU) which we hypothesised may affect the length of stay (LOS) in ICU or in hospital. In this review, we identified and critically appraised the literature on the effect of exogenous melatonin and melatonin receptor agonists on the ICU and/or hospital LOS among adults admitted to the ICU.
Methods: Six electronic databases and three trial registries were searched for randomised controlled trials (RCTs).
Emerging pharmacological strategies for the treatment of cannabis use disorder.
Expert Opin Pharmacother
September 2025
Department of Psychiatry, University of Calgary.
Introduction: Cannabis use disorder (CUD) is a growing global health concern, with limited pharmacological treatments currently available despite increasing prevalence and legalization trends.
Areas Covered: This review explores the landscape of pharmacotherapies for CUD, including both repurposed agents and emerging investigational compounds. We summarize findings from recent systematic reviews and meta-analyses, with attention to mechanisms of action and clinical relevance.