ArticlePloS one2020
Development of the first in vivo GPR17 ligand through an iterative drug discovery pipeline: A novel disease-modifying strategy for multiple sclerosis.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Rethinking MS Therapeutics: From Disease Pathogenesis Mechanisms to AI-Driven Drug Discovery.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Selective GPR17 antagonism enhances structural and functional recovery in animal models of demyelination.PloS one · 2026Article
- The GPR17 agonist galinex restores oligodendrocyte maturation under inflammatory conditions.Frontiers in pharmacology · 2026Article
- Orphan GPCRs in Neurodegenerative Disorders: Integrating Structural Biology and Drug Discovery Approaches.Current issues in molecular biology · 2024Review
- Review
- Exploring orphan GPCRs in neurodegenerative diseases.Frontiers in pharmacology · 2024Review
- Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach-A Comprehensive Narrative Review.International journal of molecular sciences · 2023Review
- G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.Signal transduction and targeted therapy · 2023Review
- Involvement of GPR17 in Neuronal Fibre Outgrowth.International journal of molecular sciences · 2021Article
- Oligodendrocyte precursor cell maturation: role of adenosine receptors.Neural regeneration research · 2021Review
- Targeting Orphan G Protein-Coupled Receptor 17 with T0 Ligand Impairs Glioblastoma Growth.Cancers · 2021Article
- Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain.International journal of molecular sciences · 2021Review
- The Distribution of GPR17-Expressing Cells Correlates with White Matter Inflammation Status in Brain Tissues of Multiple Sclerosis Patients.International journal of molecular sciences · 2021Article
- Article
- Oligodendrocyte Dysfunction in Amyotrophic Lateral Sclerosis: Mechanisms and Therapeutic Perspectives.Cells · 2021Review
- NovelFrontiers in cellular neuroscience · 2021Review
- Strategies for Oligodendrocyte and Myelin Repair in Traumatic CNS Injury.Frontiers in cellular neuroscience · 2020Review
- Purinergic Receptors on Oligodendrocyte Progenitors: Promising Targets for Myelin Repair in Multiple Sclerosis?Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The GPR17 receptor, expressed on oligodendroglial precursors (OPCs, the myelin producing cells), has emerged as an attractive target for a pro-myelinating strategy in multiple sclerosis (MS). However, the proof-of-concept that selective GPR17 ligands actually exert protective activity in vivo is still missing. Here, we exploited an iterative drug discovery pipeline to prioritize novel and selective GPR17 pro-myelinating agents out of more than 1,000,000 compounds. We first performed an in silico high-throughput screening on GPR17 structural model to identify three chemically-diverse ligand families that were then combinatorially exploded and refined. Top-scoring compounds were sequentially tested on reference pharmacological in vitro assays with increasing complexity, ending with myelinating OPC-neuron co-cultures. Successful ligands were filtered through in silico simulations of metabolism and pharmacokinetics, to select the most promising hits, whose dose and ability to target the central nervous system were then determined in vivo. Finally, we show that, when administered according to a preventive protocol, one of them (named by us as galinex) is able to significantly delay the onset of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. This outcome validates the predictivity of our pipeline to identify novel MS-modifying agents.
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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.