ABSTRACT
Introduction
Protein kinase B (Akt), an essential protein in the PI3K/Akt/mTOR signaling pathway, plays a crucial role in tumor progression. Over the past two years, different types of Akt modulators have continued to emerge in the patent literature.
Areas covered
This review focuses on the patent literature covering small molecule inhibitors, peptides, PROTACs, and antisense nucleic acids targetingAkt from 2020 to present. Also, we discuss the outcomes of several clinical trials, combination strategies for different mechanisms, and the application of Akt regulators in other non-oncology indications.Our search for relevant information was conducted using various databases, including the European Patent Office, SciFinder, andPubMed, from 01.2020 to 04.2023.
Expert opinion
In recent years, some combination therapeutic strategies involvingAkt inhibitors have shown promising clinical outcomes. Future research can be directed toward developing new applications of Akt inhibitors, which may have implications for other diseases beyond cancer. New attempts suggest that targeting allosteric sites may be a potential solution to the problem of isoform selectivity.Furthermore, directly knocking out Akt protein by using the degraderssuggests a promising direction for future development.
Article highlights
The recent clinical advances of Akt inhibitors are described in this article.
This review provides a comprehensive analysis of the structures and activity data of Akt inhibitors disclosed in patent applications from 2020 to present.
In addition to traditional small molecule inhibitors, PROTACs and antisense nucleic acid drugs are also described in detail in this review.
The combination of Akt inhibitors with tumor immunotherapy or other targeted therapies is emerging as a promising strategy.
The Akt pathway plays a key role in non-cancerous diseases, which may broaden the clinical application of Akt inhibitors in the future.
Declaration of interests
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.
Author contribution statement
Xiaowu Dong and Jinxin Che conceived the review work and instructed the writing. Linjie Li and Yu Guo drafted the manuscript. Yang Lu and Yaping Xu collected the references and clinical trial information in this field. Yan Lu and Xiuping Zhu revised the manuscript. All the authors have read and agreed to the published version of the manuscript.
Acknowledgments
, were created with BioRender.com.
Data availability statement
The authors confirm that the data supporting the findings of this study are available in the article from PubMed at https://pubmed.ncbi.nlm.nih.gov. The patent and clinical data were derived from the following resources available in the public domain, SciFinder at https://scifinder-n.cas.org, European Patent Office at https://www.epo.org/and Clinical Trials.gov at https://clinicaltrials.gov/.