Steroid sulfatase inhibitors: the current landscape

ABSTRACT

Introduction: Steroid sulfatase (STS) enzyme is responsible for transforming the inactive sulfate metabolites of steroid sex hormones into the active free steroids. Both the deficiency and the over-expression of STS are associated with the pathophysiology of certain diseases. This article provides the readership with a comprehensive review about STS enzyme and its recently reported inhibitors.

Areas covered: In the present article, we reviewed the structure, location, and substrates of STS enzyme, physiological functions of STS, and disease states related to over-expression or deficiency of STS enzyme. STS inhibitors reported during the last five years (2016-present) have been reviewed as well.

Expert opinion: Irosustat is the most successful STS inhibitor drug candidate so far. It is currently under investigation in clinical trials for treatment of estrogen-dependent breast cancer. Non-steroidal sulfamate is the most favorable scaffold for STS inhibitor design. They can be beneficial for the treatment of hormone-dependent cancers and neurodegenerative disorders without significant estrogenic side effects. Moreover, dual-acting molecules (inhibitors of STS + another synergistic mechanism) can be therapeutically efficient.

KEYWORDS:

• Hormone-dependent cancer
• steroid sulfatase
• STS enzyme
• STS inhibitors

Article highlights

• Biological features and physiological functions of STS enzyme have been reviewed.

• Relationship between STS overexpression and diseases has been reviewed.

• STS deficiency-related disorders have been reviewed.

• STS inhibitors reported from 2016 until present have been reviewed.

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.

Acknowledgment

The authors are grateful to Prof. Saeed Khan, Dean of Dubai Pharmacy College for Girls, Dubai, United Arab Emirates for his great support and encouragement during writing this article.

Additional information

Funding

This paper was not funded.