Title:Recent Advances of Small Molecule Focal Adhesion Kinase (FAK) Inhibitors as Promising Anticancer Therapeutics
Volume: 28
Issue: 34
Author(s): Pengcheng Lv*, Kun Chen and Hai-Liang Zhu
Affiliation:
- The Joint Research Center of Guangzhou University and Keele Univeristy for Gene Interference and Application, School of Life Science, Guangzhou University, Guangzhou 510006,China
Keywords:
Anticancer therapeutics, cancer target, drug design, focal adhesion kinase (FAK), small molecule FAK
inhibitors, structure-activity relationship (SAR) analysis.
Abstract: Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase involved in
the process of cell proliferation, survival, migration, and invasion. It has become a
promising therapeutic target for the treatment of human metastatic cancers due to its overexpression
and/or activation in multiple cancer types. Since FAK is emerging as a potential
cancer target because of its overexpression at both the transcriptional and translational
level in cancer, different types of FAK inhibitors with diversified scaffolds have been
discovered in the past few years. In this review, the progress of recently discovered small
molecule FAK inhibitors was summarized. Major efforts have been focused on the rational
design and synthesis of small molecule FAK inhibitors, and their structure-activity relationship
(SAR) analysis wasalso discussed. Among them, while type I inhibitors remain
as the major focuses, type II inhibitors and novel allosteric FAK inhibitors (type III inhibitors)
have been developed to improve both potency and selectivity. Meanwhile, novel
strategies, such as targeting FAK using inhibitors of protein-protein interactions, were
also discovered. Lastly, some insights and perspectives on the future development of
FAK inhibitors as anticancer therapeutics have been provided.
