A patent review of mTOR inhibitors for cancer therapy (2011–2020)

ABSTRACT

Introduction

The mammalian target of rapamycin (mTOR) kinase is a central component in the PI3K/Akt/mTOR pathway and plays a crucial role in tumor biology, making it one appealing therapeutic target. In the past decade, the mTORi (mTOR inhibitor) development field has made great progress, with more agents entering key trials and the proposal of third-generation mTORi concept. Yet to achieve significant clinical success, combined efforts from multiple disciplines are ever needed.

Areas covered

This review focuses on the progress of mTORi development with anticancer potential from the perspective of the patent literature proposed between 2011 and 2020.

Expert opinion

The highly complex regulatory mechanism network of mTOR proposes huge challenges to the development of clinically efficient mTORis. While in-depth biological research and fundamental medchemistry research are of importance to provide guidelines for improving mTORis, new technologies to pre-diagnose applicable populations is another key to provide precise personal cancer treatment. New mTOR agents are ever needed to tackle the common problems of side effects and drug resistance.

KEYWORDS:

• mtor inhibitors
• rapalogs
• ATP-competitive
• mTOR/PI3K dual
• rapalink
• cancer treatment

Article highlights

• Aberrant mTOR kinase is commonly identified in human cancers and its inhibition proved to be promising in the treatments.

• Patents on the first-, second- and third-generation mTOR inhibitors proposed from 2011 to 2020 were collected and reviewed.

• The chemical diversity of mTORi has been significantly enriched, whilst further exploring the old scaffolds may still yield new findings.

• Due to the complicity of the mTOR mechanism network and drug resistance, the potential of mTORis to be fully accomplished in cancer therapies calls for interdisciplinary efforts.

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 work was supported by National Natural Science Foundation of China (Grant No: 22001025).