An update on PTEN modulators – a patent review

ABSTRACT

Introduction: A multitude of cellular and physiological functions have been attributed to the biological activity of PTEN (Phosphatase and tensin homolog) such as inhibiting angiogenesis, promoting apoptosis, preventing cell proliferation, and maintaining cellular homeostasis. Based on whether cell growth is needed to be initiated or to be inhibited, enhancing PTEN expression or seeking to inhibit it was pursued.

Areas covered: Here the authors provide recent updates to their previous publication on ‘PTEN modulators: A patent review’, and discuss on new specificities that affirm the therapeutic potential of PTEN in promoting neuro-regeneration, stem cell regeneration, autophagy, bone and cartilage regeneration. Also, targeting PTEN appears to be effective in developing new treatment strategies for Parkinson’s disease, Alzheimer’s disease, macular degeneration, immune disorders, asthma, arthritis, lupus, Crohn’s disease, and several cancer types.

Expert opinion: PTEN mainly inhibits the PI3k/Akt pathway. However, the PI3k/Akt pathway can be activated by other signaling proteins. Thus, novel treatment strategies that can regulate PTEN alone, or combinational treatment approaches that can induce PTEN and simultaneously affect downstream mediators in the PI3K/Akt pathway, are needed, which were not investigated in detail. Commercial interests associated with molecules that regulate PTEN are discussed here, along with limitations and new possibilities to improve them.

KEYWORDS:

• PTEN regulators
• peptides
• chemical compounds
• viral vectors
• human diseases

Article highlights

• Bisperoxovanadium compounds and PAP and TGN peptides inhibit PTEN to promote neuro-regeneration in injured nerves.

• AMPK activators induce expression of PTEN to prevent progression of age-related macular degeneration.

• SF1670 increases the stem cell population by inhibiting PTEN and assists in the treatment of hematological malignancies.

• PTEN agonistic peptides prevent neuroinflammation, generalized pain and migraines.

• PINK1 promotes autophagy and is indicated in the treatment of immunological diseases.

• Nelfinavir, Metformin and Rosuvastatin combined treatment reduces genetic aberrations in PTEN and affects glioma cell survival.

This box summarizes key points contained in the article.

Acknowledgments

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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

Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number [R01HL128063] to DKA, and Creighton University LB692 Clinical & Translational Research Grant to CSB.