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Targeting Death-Associated Protein Kinases for Treatment of Human Diseases: Recent Advances and Future Directions

Lan Zhang1, Boqin Luo1, Yingying Lu1

  • 1Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.

Journal of Medicinal Chemistry
|January 16, 2023
PubMed

Insights

The death-associated protein kinase (DAPK) family regulates cell death and is implicated in human diseases. This perspective reviews DAPK structure, function, disease roles, and small-molecule inhibitors for future drug development.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cell Biology

Background:

  • The death-associated protein kinase (DAPK) family is a group of serine/threonine kinases involved in regulating cell death.
  • This family includes five members: DAPK1, DAPK2, DAPK3, DRAK1, and DRAK2, all sharing a conserved kinase domain but differing in other regions.
  • DAPKs are recognized for their crucial roles in human disease development and regulation.

Purpose of the Study:

  • To provide a comprehensive overview of the DAPK family's structure and biological functions.
  • To explore the involvement of DAPKs in various human diseases.
  • To summarize the current landscape of small-molecule inhibitors targeting DAPKs and inform future therapeutic strategies.

Main Methods:

  • Literature review and synthesis of existing research on DAPK family members.
  • Analysis of structural and functional data for DAPK proteins.
  • Compilation of information on DAPK roles in disease pathogenesis.
  • Survey of reported small-molecule inhibitors targeting the DAPK family.

Main Results:

  • Detailed discussion on the structural characteristics and conserved kinase domains of DAPK family members.
  • Elucidation of the diverse biological functions mediated by DAPKs, particularly in cell death pathways.
  • Highlighting the significant implications of DAPK dysregulation in human diseases.
  • Identification of a limited number of existing small-molecule inhibitors, underscoring a gap in therapeutic development.

Conclusions:

  • The DAPK family represents a critical node in cellular processes, especially cell death, and is linked to human pathology.
  • The limited availability of specific inhibitors necessitates further research and development in this area.
  • This perspective serves as a valuable resource for advancing DAPK-targeted drug discovery and therapeutic interventions.

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