Glutaminase inhibitors: a patent review

ABSTRACT

Introduction: The kidney-type glutaminase (GLS) controlling the first step of glutamine metabolism is overexpressed in many cancer cells. Targeting inhibition of GLS shows obvious inhibitory effects on cancer cell proliferation. Therefore, extensive research and development of GLS inhibitors have been carried out in industrial and academic institutions over the past decade to address this unmet medical need.

Areas covered: This review covers researches and patent literatures in the field of discovery and development of small molecule inhibitors of GLS for cancer therapy over the past 16 years.

Expert opinion: The detailed ligand-receptor interaction information from their complex structure not only guides the rational drug design, but also facilitates in silico structure-based virtual ligand screening of novel GLS inhibitors. Multi-drug combination administration is of great significance both in terms of safety and efficacy.

KEYWORDS:

• Cancer
• small molecule inhibitor
• combination therapy
• kidney-type glutaminase (GLS)

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest 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 received funding from National Natural Science Foundation of China (NSFC) (grant number 81473254, 81773637, 81773594, U1703111), the Fundamental Research Fund for the Central Universities (grant number 2017KFYXJJ151).