An updated patent review of IDO1 inhibitors for cancer (2018–2022)

ABSTRACT

Introduction

Indoleamine 2,3-dioxygenase 1 (IDO1) is highly related to the immune evasion of a wide range of malignancies due to its role in the immune suppression caused by the depletion of tryptophan (Trp) and the accumulation of kynurenine (Kyn). The combination of IDO1 inhibitors with other treatments represents a promising strategy in immunotherapy, although considerable challenges lie ahead.

Areas covered

This review focuses on patent publications searched from Espacenet and Google Scholar, and related to IDO1 inhibitors with potential anti-cancer utilization during the period 2018–2022.

Expert opinion

Despite the clinical trial failure of the first-in-class IDO1 inhibitor epacadostat in combination with pembrolizumab, numerous studies have been carried on to pursue more efficient IDO1-based immune-modulating therapeutic solutions. A large number of IDO1 inhibitors with new structures and design concepts have been produced with the impetus of crystallographic studies, and have shown great research potential. The elaboration on the combination of IDO1 inhibitors with other targeting agents, the more precise selection of patients, the identification of more reliable biomarkers for evaluating the IDO1 treatment, and the investigation of possible toxicity, are critical factors to promote IDO1-based immunotherapies from bench to bedside.

KEYWORDS:

• IDO1 inhibitors
• kynurenine pathway
• anticancer
• immunotherapy

Article highlights

• The overexpression of IDO1 is responsible for the escape from immunity during the progression of many cancer types.

• Patents regarding IDO1 inhibitors with anticancer potency (2018–2022) were collected and reviewed.

• New forms of IDO1 inhibitors provide choices in the context of IDO1-based immunotherapies.

• Mechanistic research and rational trial design are still vitally needed to promote the IDO1 inhibitors from bench to bedside.

Author contribution statement

HY Qiu proposed and guided this manuscript. PF Wang drafted the manuscript.

LQ Yang, ZH Shi, and X Li retrieved patents and literature, prepared figures and tables, and also contributed to the draft.

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 funded by the Fundamental Research Funds for the Central Universities (2022CDJXY-025), and the National Science Foundation of China (22001025, 22101037).