A patent review of topoisomerase I inhibitors (2016–present)

ABSTRACT

Introduction

Topoisomerases are important targets for therapeutic improvement in the treatment of some diseases, including cancer. Inhibitors and poisons of topoisomerase I can limit the activity of this enzyme in its enzymatic cycle. This fact implies an anticancer effect of these drugs, since most cancer cells are characterized by both a higher activity of topoisomerase I and a higher replication rate compared to non-cancerous cells. Clinically approved inhibitors include camptothecin (CPT) and its derivatives. However, their limitations have encouraged different research groups to prepare new compounds, proof of which are the numerous research works and patents, some of them in the last five years.

Areas covered

This review covers patent literature on topoisomerase I inhibitors and their application published between 2016-present.

Expert opinion

The highest contribution toward patent development has been obtained from academics or small biotechnology companies. The most important fields of innovation include the preparation of prodrugs or inhibitors combined with other agents, as biocompatible polymers or antibodies. A promising development of topoisomerase I inhibitors is expected in the next years, directed to the treatment of diverse diseases, specifically toward different types of cancer and infectious diseases, among others.

KEYWORDS:

• Topoisomerase I inhibitors
• cancer
• infectious diseases

Article highlights

1. Useful TopI inhibitors in the treatment of cancer

2. Useful TopI inhibitors in the treatment of infectious diseases

3. Combination of TopI inhibitors and other units represent versatile tools for the treatment of cancer and other diseases

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, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI), Fondo Europeo de Desarrollo Regional (FEDER; RTI2018-101818-B-I00, UE), and by Gobierno Vasco, Universidad del País Vasco (GV, IT 992-16; UPV). A.S. thanks the Basque Government for a formation contract.