Selective 7-Azaindole Modulators Targeting Fyn and GSK-3β for Dual-Target Neuromodulation

Fyn proto-oncogene kinase (Fyn) and glycogen synthase kinase-3β (GSK-3β) belong to distinct branches of the protein kinase (PK) superfamily. Fyn is a member of the Src family of tyrosine kinases, whereas GSK-3β is classified within the CMGC group of serine/threonine kinases. Both play critical roles in neurodegenerative processes, and their dysregulation has been implicated in disease progression. The development of Fyn and GSK-3β inhibitors has attracted increasing research attention. The design of multitarget inhibitors represents a promising, though underexplored, therapeutic strategy. A recent study reported a series of dual selective nanomolar inhibitors based on structure-activity relationship (SAR) optimization. In-depth profiling of the lead compound's neuroprotective and modulatory properties establishes a foundation for the development of next-generation neuroregenerative therapeutics.

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Publication Details

Journal
ACS Medicinal Chemistry Letters
Published
2025-12-24
DOI
https://doi.org/10.1021/acsmedchemlett.5c00728
Primary Topic
Wnt/β-catenin signaling in development and cancer
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article
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article

Selective 7-Azaindole Modulators Targeting Fyn and GSK-3β for Dual-Target Neuromodulation

Steven H. Liang, Haofeng Shi, Yinlong Li
ACS Medicinal Chemistry Letters
Wnt/β-catenin signaling in development and cancer
article

Selective 7-Azaindole Modulators Targeting Fyn and GSK-3β for Dual-Target Neuromodulation

Steven H. Liang, Haofeng Shi, Yinlong Li
article en

Abstract

Fyn proto-oncogene kinase (Fyn) and glycogen synthase kinase-3β (GSK-3β) belong to distinct branches of the protein kinase (PK) superfamily. Fyn is a member of the Src family of tyrosine kinases, whereas GSK-3β is classified within the CMGC group of serine/threonine kinases. Both play critical roles in neurodegenerative processes, and their dysregulation has been implicated in disease progression. The development of Fyn and GSK-3β inhibitors has attracted increasing research attention. The design of multitarget inhibitors represents a promising, though underexplored, therapeutic strategy. A recent study reported a series of dual selective nanomolar inhibitors based on structure-activity relationship (SAR) optimization. In-depth profiling of the lead compound's neuroprotective and modulatory properties establishes a foundation for the development of next-generation neuroregenerative therapeutics.

ACS Medicinal Chemistry LettersVol. 17(1)
Georgia Institute of Technology (US), Emory University (US), The Wallace H. Coulter Department of Biomedical Engineering (US)
Good health and well-being
Openalex Percentile: Top 36%
Wnt/β-catenin signaling in development and cancer
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Selective 7-Azaindole Modulators Targeting Fyn and GSK-3β for Dual-Target Neuromodulation — Steven H. Liang, Haofeng Shi, et al. · ACS Medicinal Chemistry Letters (2025) | TGRS Research Map | TGRS