An updated patent review of small-molecule c-Met kinase inhibitors (2018-present)

ABSTRACT

Introduction

c-Met tyrosine kinase receptor is a high-affinity ligand of hepatocyte growth factor (HGF). c-Met is widely expressed in a variety of normal human tissues, but shows abnormally high expression, amplification or mutation in tumour tissues such as lung, gastric and breast cancers. Therefore, the use of c-Met as a target can achieve the inhibition of a series of abnormal physiological processes such as tumourigenesis, development and metastasis. A number of small molecule tyrosine kinase inhibitors targeting c-Met have been successfully marketed.

Areas covered

This article reviews recent advances in patented c-Met small molecule inhibitors and their inhibitory activity against various cancer cells from 2018 to date.

Expert opinion

To date, small molecule inhibitors targeting c-Met have demonstrated impressive therapeutic efficacy in the clinical setting. Most recent patents have focused on addressing the direction of c-Met amplification and overexpression. Despite the great success in the development of selective c-Met inhibitors, the effects of bypass secretion and mutagenesis have led to a need for new c-Met small molecule inhibitors that are safe, efficient, selective and less toxic with novel structures and effective against other targets.

KEYWORDS:

• Cancer therapy
• c-Met inhibitors
• small-molecule inhibitor
• patent review

Article highlights

• c-Met inhibitors are a promising area of anti-cancer drug development and some inhibitors have already been approved by the FDA.

• This paper reviews patent applications for c-Met small molecule inhibitors from 2018 to the present from 20 companies and institutions.

• Provides in vitro kinase and cell analysis data of all representative compounds and provides an overall analysis.

• In view of the frequent occurrence of drug resistance, the development of novel c-Met multi-target inhibitors is of great significance and will become a trend.

Declaration of interest

The authors have no 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.

Additional information

Funding

This study was funded by National Natural Science Foundation of China [82160659], Natural Science Foundation of Jiangxi, China [20202BABL216076], Science and Technology Project Founded by the Education Department of Jiangxi Province, China [GJJ180628, GJJ190583], Youth talent support program [2019QNBJRC008] and Nanchang Key Laboratory of Molecular Targeted Anticancer Drug Design and Evaluation [2019-NCZDSY-007].