A patent review of Monoacylglycerol Lipase (MAGL) inhibitors (2013-2017)

ABSTRACT

Introduction: Monoacylglycerol lipase is a serine hydrolase that plays a major role in the degradation of the endocannabinoid 2-arachidonoylglycerol. Because of this key role, selective inactivation of MAGL represents an interesting approach to obtain desirable effects in several diseases. Furthermore, MAGL is upregulated in cancer cells and primary tumors and its inhibition in aggressive breast, ovarian, and melanoma cancer cells impairs cell migration, invasiveness, and tumorigenicity.

Areas covered: This review covers patent literature on MAGL inhibitors and their applications published from 2013 to 2017.

Expert opinion: MAGL inhibition has gained considerable importance in many therapeutic fields and one compound has been subjected to Phase I studies. Even if a reasonable number of patents have been recently reported, novel MAGL inhibitors are still required, especially novel chemical classes displaying a reversible mechanism of action.

KEYWORDS:

• MAGL
• inhibitors
• cannabinoids
• cancer
• neurodegenerative disorders

Article Highlights

• Recently patented MAGL inhibitors and their use, as described in reports made from 2013–2017 are discussed.

• MAGL inhibitors have gained a prominent role for indirect cannabinoid receptor activation and lipid signals.

• MAGL inhibition is applied in the area of pain and inflammation, metabolic disorders (such as obesity and diabetes), neurodegenerative pathologies (such as Alzheimer’s disease), anxiety and epilepsy.

• MAGL is a valid target to impair cell migration, invasiveness, and tumorigenicity in different aggressive cancer cells.

• Covalent vs non-covalent MAGL inhibitors are compared and discussed.

This box summarizes key points contained in the article.

Declaration of interest

Isabella Caliguri is affiliated with the National Cancer Institute and Center for Molecular Biomedicine, Aviano. The authors have no other 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 apart from those disclosed.