ArticleMolecular pain
Novel RET agonist for the treatment of experimental neuropathies.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Translational insights into canine dorsal root ganglia cell types using cross-species comparisons.bioRxiv : the preprint server for biology · 2026Article
- IGSF10 is a RET antagonist regulating Ewing sarcoma growth and GnRH neuron migration.Cell reports · 2025Article
- Integrating artificial intelligence and optogenetics for Parkinson's disease diagnosis and therapeutics in male mice.Nature communications · 2025Article
- Schwann cells modulate nociception in neurofibromatosis 1.JCI insight · 2024Article
- Biological ActivityBiomacromolecules · 2023Article
- Neurotrophic factors in the physiology of motor neurons and their role in the pathobiology and therapeutic approach to amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2023Review
- Is activation of GDNF/RET signaling the answer for successful treatment of Parkinson's disease? A discussion of data from the culture dish to the clinic.Neural regeneration research · 2022Review
- The Neuropeptide Cortistatin Alleviates Neuropathic Pain in Experimental Models of Peripheral Nerve Injury.Pharmaceutics · 2021Article
- Glial Cell Line-Derived Neurotrophic Factor Family Ligands, Players at the Interface of Neuroinflammation and Neuroprotection: Focus Onto the Glia.Frontiers in cellular neuroscience · 2021Review
- Neuroprotective Potential of a Small Molecule RET Agonist in Cultured Dopamine Neurons and Hemiparkinsonian Rats.Journal of Parkinson's disease · 2021Article
- RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer.International journal of molecular sciences · 2020Review
- Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) alleviate symptoms of experimental neuropathy, protect and stimulate regeneration of sensory neurons in animal models of neuropathic pain, and restore their functional activity. However, clinical development of GFL proteins is complicated by their poor pharmacokinetic properties and multiple effects mediated by several receptors. Previously, we have identified a small molecule that selectively activates the major signal transduction unit of the GFL receptor complex, receptor tyrosine kinase RET, as an alternative to GFLs, for the treatment of neuropathic pain. We then introduced a series of chemical changes to improve the biological activity of these compounds and tested an optimized compound named BT44 in a panel of biological assays. BT44 efficiently and selectively stimulated the GFL receptor RET and activated the intracellular mitogene-activated protein kinase/extracellular signal-regulated kinase pathway in immortalized cells. In cultured sensory neurons, BT44 stimulated neurite outgrowth with an efficacy comparable to that of GFLs. BT44 alleviated mechanical hypersensitivity in surgery- and diabetes-induced rat models of neuropathic pain. In addition, BT44 normalized, to a certain degree, the expression of nociception-related neuronal markers which were altered by spinal nerve ligation, the neuropathy model used in this study. Our results suggest that the GFL mimetic BT44 is a promising new lead for the development of novel disease-modifying agents for the treatment of neuropathy and neuropathic pain.
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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.