Fyn kinase in brain diseases and cancer: the search for inhibitors

Curr Med Chem. 2011;18(19):2921-42. doi: 10.2174/092986711796150531.

Abstract

Fyn is a non-receptor tyrosine kinase belonging to the Src family kinases. It has been shown to play important roles in neuronal functions, including myelination and oligodendrocytes formation, and in inflammatory processes. It has also demonstrated its involvement in signaling pathways that lead to severe brain pathologies, such as Alzheimer's and Parkinson's diseases. Moreover, Fyn is upregulated in some malignancies. Experimental studies demonstrated that Fyn inhibition could be useful in the disruption of metabolic processes involved in cancer neurodegenerative diseases. Unfortunately, no specific Fyn inhibitor has been discovered till today, active compounds on other members of Src family or on different tyrosine kinases have also been reported. However, multitargeted inhibitors might be endowed with therapeutic potential. Indeed, as increasingly reported, also a not completely selective inhibitor of a specific protein could be therapeutically useful, affecting a number of cell pathways involved especially in cancer development. In this review, we report some examples of small molecule tyrosine kinase inhibitors for which data on Fyn inhibition, both in enzymatic and in cell assays, have been reported, with the aim of giving information as starting point for the researchers working in this field.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Brain / drug effects
  • Brain / enzymology
  • Brain Diseases / drug therapy*
  • Brain Diseases / enzymology*
  • Humans
  • Molecular Sequence Data
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology*
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-fyn / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-fyn / chemistry
  • Proto-Oncogene Proteins c-fyn / metabolism*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-fyn