Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential anti-diabetes agents: patent review (2015-2018)

ABSTRACT

Introduction: Protein tyrosine phosphatase 1B (PTP1B) inhibition has been recommended as a crucial strategy to enhance insulin sensitivity in various cells and this fact is supported by human genetic data. PTP1B inhibitors improve the sensitivity of the insulin receptor and have the ability to cure insulin resistance-related diseases. In the latter years, targeting PTP1B inhibitors is being considered an attractive target to treat T2DM and therefore libraries of PTP1B inhibitors are being suggested as potent antidiabetic drugs.

Areas covered: This review provides an overview of published patents from January 2015 to December 2018. The review describes the effectiveness of potent PTP1B inhibitors as pharmaceutical agents to treat type 2 diabetes.

Expert opinion: Enormous developments have been made in PTP1B drug discovery which describes progress in natural products, synthetic heterocyclic scaffolds or heterocyclic hybrid compounds. Various protocols are being followed to boost the pharmacological effects of PTP1B inhibitors. Moreover these new advancements suggest that it is possible to get small-molecule PTP1B inhibitors with the required potency and selectivity. Furthermore, future endevours via an integrated strategy of using medicinal chemistry and structural biology will hopefully result in potent and selective PTP1B inhibitors as well as safer and more effective orally available drugs.

KEYWORDS:

• PTP1B
• natural inhibitors
• synthetic inhibitor
• diabetes
• selectivity

Article highlights

• PTP1B plays an promising role in the insulin signaling pathway.

• PTP1B inhibitors have been suggested as promising antidiabetic drugs.

• Potent PTP1B inhibitors demonstrated effects in the low nanomolar range of IC₅₀ values.

• Number of compounds were synthesized having heterocyclic scaffolds which displayed potent PTP1B inhibition.

Converted PTP1B inhibitors boost the insulin sensitivity and have the ability to cure T2DM.

This box summarizes key points contained in the article.

Acknowledgments

H Hussain is thankful to the Alexander von Humboldt Foundation for its generous support in providing the opportunity to do work in Germany which facilitated the writing of this review.

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 paper was not funded.