ArticleJournal of medicinal chemistry2025
Exploration of the Neuromodulatory Properties of Fyn and GSK-3β Kinases Exploiting 7-Azaindole-Based Inhibitors.
Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- 7-azaindole as privileged scaffold: Advances in drug design and structural modification.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Imidazo[2,1-Antibiotics (Basel, Switzerland) · 2026Article
- A Polypharmacology-Driven Approach to Alzheimer's Disease and Tauopathies: Rational Design, Synthesis and Characterization of Amino-Pyrazole-Based Multikinase (GSK-3β/FYN-α/DYRK1A) Inhibitors.Journal of medicinal chemistry · 2026Article
- Neuroprotective efficacy of hentriacontane against rotenone-induced apoptosis in SH-SY5Y cells: In silico and in vitro evidence of GSK3β association.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Selective 7‑Azaindole Modulators Targeting Fyn and GSK-3β for Dual-Target Neuromodulation.ACS medicinal chemistry letters · 2026Article
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Authors and funding
16 authors.
Funding
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Abstract
The lack of efficient treatments and reliable biomarkers for neurodegenerative diseases requires the development of a late-stage powerful therapy. To this aim, we focused on Fyn and GSK-3β because both kinases are strictly involved in regulating neurodevelopmental processes, besides orchestrating neurotoxic aggregates' deposition and neuroinflammatory processes development. Based on these premises, we developed dual kinase inhibitors to verify at the cellular level the suitability of Fyn and GSK-3β modulation in pursuing the recovery of neural trophism paired to the activation of a neuroprotective profile. Starting from the mild inhibitory potency of the 3-aminothiazole-7-azaindole scaffold, we identified nanomolar dual and selective inhibitors among the kinases of interest. In-depth biological evaluations were performed with the best compounds of the series to assess the neuroprotective and neuromodulatory properties, like enabling neurogenesis or glial polarization, as well as triggering immunomodulation with different patterns relating to their inhibitory profile, setting the stage for potential development of neuroregenerative treatments.
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