FAK inhibitors in Cancer, a patent review

ABSTRACT

Introduction: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes at sites of cell adhesion to the extracellular matrix (ECM) and mediates signalling events downstream of integrin engagement of the ECM. FAK is known to regulate cell survival, proliferation and migration.

Areas covered: FAK expression has also been shown to be up-regulated in many cancer types. Previous study also indicates that FAK-mediated signaling and functions are intrinsically involved in the progression of tumor aggressiveness, suggesting that FAK is a promising target for anticancer therapies. Small molecule FAK inhibitors have been developed and are being tested in clinical phase trials.

Expert Opinion: These inhibitors have demonstrated to be effective by inducing tumor cell apoptosis in addition to reducing metastasis and angiogenesis. In this review, we give updates on the design, synthesis and structure-activity relationship analysis of small molecule FAK inhibitors discovered from 2015 until now. We also review the FAK inhibitors that are in clinical development and highlight the future prospects.

KEYWORDS:

• Anticancer agents
• cancer therapy
• focal adhesion kinase (FAK)
• non-receptor tyrosine kinase
• small molecule FAK inhibitors

Article highlights

• FAK expression has also been shown to be up-regulated in many cancer types, so FAK is a promising target for anticancer therapies.

• This review details the design, synthesis and structure-activity relationship analysis of small molecule FAK inhibitors discovered from 2015 until now.

• FAK inhibitors that are in clinical development were discussed and future prospects were highlighted.

Acknowledgments

The work was financed by a grant from China Major Projects on Control and Rectification of Water Body Pollution (2017ZX07602-002).

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper has not been funded.