Background: Focal adhesion kinase (Fak) is a cytoplasmic protein tyrosine kinase
overexpressed and activated in different solid cancers; it has shown an important
role in metastasis formation, cell migration, invasion and angiogenesis and consequently
it has been proposed as a potential target in cancer therapy, particularly in a metastatic
phase. In recent years, different investigations have highlighted the importance of new
Fak inhibitors as potential anti-cancer drugs, but other studies evidenced its role in different
pathologies related to the cardiac function or viral infection.
Methods: An extensive bibliographic research (104 references) has been done concerning
the structure of Fak, its importance in tumor development, but also in other pathologies
currently under study. The compounds currently subjected to clinical studies were
therefore treated using the appropriate databases. Finally, the main chemical scaffolds
currently under preclinical investigation were analyzed, focusing on their molecular structures
and on the activity structure relationships (SAR).
Results: At the moment, only a few reversible ATP-competitive inhibitors are under investigation
in pre-clinical studies and clinical trials. Other compounds, with different
chemical scaffolds, are investigated to obtain more active and selective Fak inhibitors.
This mini-review is a summary of different Fak functions in cancer and other pathologies;
the compounds today in clinical trials and the recent chemical scaffolds (also included
in patents) giving the most interesting results are investigated. In addition, PROTAC
molecules are reported.
Conclusion: All reported results evidenced that additional studies are necessary to design
and synthesize new selective and more active compounds, although promising information
has been obtained from associations between Fak inhibitors and other different anti-
cancer drugs. In addition, the other important roles evidenced, both at the nuclear level
and in non-cancerous cells, make this protein an increasingly important target in pharmaceutical