Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: a patent review (2014-present)

ABSTRACT

Introduction: EGFR is the receptor for epidermal growth factor (EGF) and belongs to the protein tyrosine kinase (PTK) receptor. It is closely related to the inhibition of tumor cell proliferation, invasion, and apoptosis. Overexpression or mutation activation of EGFR is involved in the development of many human malignancies, especially non-small cell lung cancer (NSCLC). At present, numerous small molecule tyrosine kinase inhibitors (TKIs) have been developed to target the ATP-binding region of EGFR, aiming to develop selective and effective inhibitors for the treatment of NSCLC against EGFR mutants.

Areas covered: This review covers the latest progress in the patented EGFR inhibitors and the inhibition activity against NSCLC from 2014 to present.

Expert opinion: EGFR is an important anti-tumor target, and small molecule inhibitors targeting EGFR have become important biologically active compounds for the treatment of cancer, especially against NSCLC. Among the recent patents available, great majority of them focus on selective inhibitors of EGFR mutants. Although great achievements have been made in the development of selective EGFR inhibitors, there is still an urgent need to discover new EGFR inhibitors which are safe, efficient, selective, and low-toxic to avoid the adverse pharmacokinetics caused by wild-type EGFR feature.

KEYWORDS:

• Cancer
• EGFR
• EGFR-TKIs
• NSCLC
• resistance mutation

Article highlights

• Small molecule tyrosine kinase inhibitors targeting EGFR are a promising area in the development of anticancer drugs and some inhibitors have been approved by the FDA.

• This paper reviewed the development progress of recent patent documents (2014-present) on EGFR inhibitors.

• Exploration of compounds containing various representative chemical scaffolds and their available data have led to the discovery of a variety of effective EGFR inhibitors.

• In view of the side effects of drug resistance, the development of selective, potent, and novel inhibitors of targeted mutant EGFR has become a very promising method to combat non-small cell lung cancer, which is of great significance and will become a trend.

This box summarizes key points contained in the article.

Reviewer disclosures

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

disclose.

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.

Additional information

Funding

This study was funded by National Natural Science Foundation of China [21662014]; Natural Science Foundation of Jiangxi, China [20181ACB20025, 20181BBG70003]; Science and Technology Project Founded by the Education Department of Jiangxi Province, China [GJJ180628, GJJ190583] and Nanchang Key Laboratory of Molecular Targeted Anticancer Drug Design and Evaluation [2019-NCZDSY-007].