An updated patent review of Akt inhibitors (2016-present)

ABSTRACT

Introduction: Akt is a widely known serine threonine kinase involved in a series of critical cellular pathways like cell survival and proliferation. With the development of small-molecule Akt inhibitors, new strategies such as covalent, peptide-based, and PROTAC (Proteolysis Targeting Chimera) strategies have also been used the design of Akt inhibitors. On the other hand, due to the specificity of the Akt pathway, the use of Akt modulators in combination therapy and immunotherapy has been disclosed in the past 5 years.

Areas covered: This review focuses on the patent literature covering small-molecule inhibitors of Akt kinase and their applications from 2016–present.

Expert opinion: Although Akt inhibitors’ progress has been somewhat slow over the past five years, new strategies still provide new opportunities for the development of Akt inhibitors. Combination with Akt pathway inhibitors for tumor therapy has also been widely disclosed in patents in the last 5 years. Notably, combination strategies of Akt inhibitors and immunotherapy have started to emerge in recent years. While the clinical indications of Akt modulators should not be limited to anti-cancer, it is still worth trying the treatment of other diseases. Within the next years, current drug development around Akt inhibitors should be fascinating.

KEYWORDS:

• Akt
• inhibitors
• patents
• cancer
• clinical trial
• new strategies
• indications

Article highlights

• The structures of Akt inhibitors disclosed in patents from 2016 to 2020 are reviewed in this article.

• New strategies such as covalent, peptide-based, and PROTAC strategies have been used in the design of Akt inhibitors.

• Combination therapies may provide new opportunities for the development of Akt inhibitors.

• Immunotherapy related to Akt inhibitors have started to emerge in recent years.

• The clinical indications of Akt modulators are not only limited to anti-tumor therapy but play more important roles in some other indications.

This box summarizes key points contained in the article.

Acknowledgments

Figure 6, Figure 8 and Figure 9 were created with BioRender.com. Figure 6 was adapted from “PROTAC: Proteolytic Targeting Chimera”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates. Figure 9 was adapted from “Novel Pharmacotherapies for Diabetic Macular Edema (DME)”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates.

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 grant from the National Natural Science Foundation of China (81973172, 82003579), Natural Science Foundation of Zhejiang Province (LR21H300003), and National Major Scientific and Technological Special Project for ‘Significant New Drugs Development’ (2018ZX09711002–007, 2018ZX09711002–011–023).