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Review

c-Met kinase inhibitors: an update patent review (2014-2017)

, & ORCID Icon
Pages 25-41
Received 09 Jul 2018
Accepted 21 Nov 2018
Accepted author version posted online: 24 Nov 2018
Published online: 12 Dec 2018
 

ABSTRACT

Introduction: The receptor tyrosine kinase c-Met is involved in the formation, metastasis and invasion of various malignant tumors thus it has been an attractive target for anti-tumor drug designing. Many compositions targeting c-Met have been developed in pharmaceutical industry for cancer therapy and some of them are in clinical study now. Among them, Crizotinib was the first small molecular inhibitor approved by FDA in 2011.

Areas covered: This review briefly summarizes the signal transduction pathway about c-Met, its role in oncogenesis, most recent patents of small-molecule inhibitors and antibodies of c-Met from 2014 to 2017.

Expert opinion: To date, some c-Met inhibitors have been launched in the market. In addition, their clinical performances have shown encouraging value in cancer therapy. Many potential agents are still in preclinical or clinical study now and achieve some promising progressions. Some patients have developed resistance to c-Met inhibitors which results in the need to develop inhibitors with novel structures. Development of several potent drugs also tends to be pharmacodynamically active against multiple targets.

Article highlights

  • Tyrosine-protein kinase Met (c-Met) inhibitors are an efficient class of tumor therapy currently under clinical investigation.

  • This article covers new c-Met patent applications between 2014 and 2017 reported by 26 companies and institutions.

  • Structures and the efficacies such as the IC50 values of the representative compounds in various assays are provided.

  • The selectivity and structures of these inhibitors are further discussed in the conclusion.

This box summarizes key points contained in the article.

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

Additional information

Funding

This work was supported by National Natural Science Foundation of China (Grant No. 21102182), Natural Science Foundation of Jiangsu Province (Grant No. BK2012760), College Students Innovation Project for the R&D of Novel Drugs (Grant No. J1310032), National College Students' innovation and entrepreneurship training program (Grant No. 201810316057G), and Excellent Science and Technology Innovation Team of Jiangsu Province Universities in 2015, China.

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