2. Academic Validation
  3. Selective 7‑Azaindole Modulators Targeting Fyn and GSK-3β for Dual-Target Neuromodulation

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

  • ACS Med Chem Lett. 2025 Dec 24;17(1):32-35. doi: 10.1021/acsmedchemlett.5c00728.
Haofeng Shi 1,  Yinlong Li 1,  Steven H Liang 1 2
Affiliations

Affiliations

  • 1 Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States.
  • 2 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United States.
PMID: 41531958 DOI: 10.1021/acsmedchemlett.5c00728
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.

Keywords

Fyn proto-oncogene kinase; glycogen synthase kinase 3β; neurodegenerative diseases; structure−activity relationship.

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