Optimization techniques for novel c-Met kinase inhibitors

ABSTRACT

Introduction: c-Met kinase plays an important part in the regulation of cell growth, invasion and anti-apoptosis. This enzyme is also an important target in cancer treatment. Through structural optimization and structure-activity studies of drugs currently on the market and those still in clinical trials, a great number of novel c-Met kinase inhibitors have been developed. This review focuses on recent developments in research regarding novel c-Met inhibitor synthesis, optimization, and structure-activity relationship (SAR) studies.

Area covered: In this review, the authors discuss the representative research of c-Met inhibitors published in recent years. Furthermore, it provides background research of c-Met kinase inhibitors, the introduction of drugs on the market and in clinical research, and the research progress of novel small molecule inhibitors. In particular, this review emphasizes the important role of ‘5-atoms linker’ in the design of some novel c-Met enzyme inhibitors.

Expert opinion: Discovering novel c-Met kinase inhibitors via natural product chemistry may become a new research field. Though it is difficult, the key to developing better c-Met kinase inhibitors is structural optimization.

KEYWORDS:

• Cancer
• c-Met
• optimization
• inhibitors
• hepatocyte growth factor

Acknowledgement

Authors thank Huairuo Xu from International Department American Division, Nanjing Jinling High School, Nanjing, China for her suggestions to improve the manuscript.

Article highlights

• C-Met inhibitors play an important part in cancer treatment.

• Many c-Met inhibitors have been developed in recent years. They can be categorized into different types based on their structures.

• Computer-aided drug design and the modification of ‘5-atoms linker’ can be used in c-Met inhibitor development.

• The development of c-Met inhibitors requires multidisciplinary cooperation. Structural biologists may provide new active sites for c-Met kinase.

• It is possible that more effective c-Met inhibitors can be obtained via natural products screening and optimization.

This box summarizes key points contained in the article.

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

One referee declares that they own stocks with Octimet and Metis.

Additional information

Funding

This manuscript was not funded.