Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2016–2019)

ABSTRACT

Introduction

Glycogen synthase kinase 3 (GSK-3) is a constitutively active, ubiquitous expressed ser/thr kinase that is involved in a large number of signaling pathways. GSK-3 is a key target of a remarkably large number of cellular processes and diseases such as diabetes type II, cancer, immune disorder, neurodegenerative pathologies among others diseases and surely in regenerative medicine. During the last decades the scientific community has been working to understand the role of GSK-3 with the aim in mind of design efficient and selectivity GSK-3 inhibitors (GSK3i). However so far clinical and preclinical GSK3i have been both sub-optimal regarding potency, poor GSK-3 selectivity over other CNS targets and closely related kinases, low CNS exposure, and chronic toxicity. Research into GSK inhibitors relay primarily on identification of the new use of the know GSK3i and the development of them in order to improve selectivity and toxicity.

Areas covered

This review covers patent literature on GSK3i and their application published between 2016 and 2019.

Expert opinion

Thanks to the past, present, and future research, in the next few years we will see progress in the treatment of some diseases with GSK3i, for instance in regenerative medicine immunotherapy applications among others.

KEYWORDS:

• GSK-3 inhibitors
• Alzheimer’s disease
• neurodegenerative diseases
• regenerative medicine
• immunotherapy

Article highlights

1. GSK-3 inhibitors have gained a prominent role in regenerative medicine to modulate human stem cells and iPSC

2. The synergy effect of GSK-3 inhibitors and well-known anticancer drugs show promising results in different cancer

3. New therapeutic uses for GSK-3 inhibitors are being discovered continuously

4. New inhibitors are being developed trying to improve selectivity and toxicity

This box summarizes key points contained in the article.

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 the Ministerio de Ciencia e Innovación under Grant RTI2018-096100B-100.