FAK inhibitors in cancer, a patent review – an update on progress

ABSTRACT

Introduction

Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation.

Areas covered

There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research.

Expert Opinion

FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure–activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.

KEYWORDS:

• Focal adhesion kinase (FAK)
• non-receptor tyrosine kinase
• therapeutic target
• chemotherapeutic FAK inhibitors
• cancer treatment

Article highlights

• Targeting FAK in tumors has emerged as a credible lethality mechanism.

• There are many promising scaffolds that can be developed into potent leads with structural modifications to maximize their potential.

• Highly selective inhibitors decrease the side effects efficiently, while multi-target inhibitors can not only bind with FAK to exert inhibitory effects, but also interact with other targets, thereby synergistically promoting anti-cancer effects.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Ya-Xi Ye: Investigation, Writing – Original Draft;

Yu-Yao Cao: Data collation;

Li-Sheng Xu: Funding acquisition;

Hai-Chao Wang: Funding acquisition;

Xin-Hua Liu: Project administration;

Hai-Liang Zhu: Supervision, Funding acquisition;

Additional information

Funding

This work was supported by Research Initiation Fund Project of Suzhou University (2022BSK032), Key Project of Anhui Provincial Department of Education Natural Science Research (2023AH052249), the Suzhou University’s 2021 school-level scientific research platform (2021XJPT34), Suzhou University Research Development Fund Project (2023fzjj01).