Background

The enzyme monoacylglycerol lipase (MAGL), which is part of the endocannabinoid system (ECS), has therapeutic potential for the treatment of various types of pathologies, as it has been demonstrated by numerous studies. In particular, the inhibition of the catalytic activity of MAGL represents a promising pharmacological strategy to activate the ECS without incurring in the adverse effects typically associated with the direct activation of cannabinoid receptors. Furthermore, it has been demonstrated that the genetic or pharmacological depletion of MAGL activity has a neuroprotective effect in various animal models of demyelinating diseases (such as multiple sclerosis and other neurodegenerative diseases). In addition, MAGL has an important role in the development of invasive tumours, being involved in lipid metabolism, which has been considered a fundamental target in the treatment of tumours. Despite the development of potent MAGL inhibitors with different chemical structures in recent years, their number is still quite limited and, above all, most of these compounds are characterized by irreversible inhibition of the enzyme, thus compromising the basal functioning of ECS.

Technology Overview

The strengths of the MAGL inhibitors here presented lie in the powerfulness and, at the same time, reversibility of the mechanism of action, mediated in particular by non-covalent bonds.

Indeed, on one hand in vitro screening of these compounds demonstrated activity in the nanomolar range and in the other reversibility tests and kinetic evaluations confirmed the innovation of these compounds.

Last but not least, the proposed MAGL inhibitors can be advantageously used to prevent and/or treat any condition that could be improved by the inhibition of MAGL, such as serious pathological conditions of neurodegenerative inflammation and tumours (such as colorectal cancer, breast cancer and ovarian cancer).

Further Details

https://doi.org/10.1016/j.ijpharm.2021.121374

Stage of Development

TRL (Technology Readiness Level): 3-4.

Benefits

Reversibility
Strong reduction of side effects
High effectiveness tested in various tumour cell lines
Exploitable against many neurodegenerative pathologies
One of the few efficient and reversable MAGL inhibitors based by non-covalent bonding

Applications

Innovative and less harmful pharmaceutical compositions for the treatment of neurodegenerative pathologies in severe conditions
Innovative and less harmful pharmaceutical compositions for the treatment of tumours

Opportunity

Patent in collaboration with University of Pisa.

Open to collaborative projects to further develop the technology and/or licensing.

Reversible Monoacylglycerol Lipase (MAGL) Inhibitors for Neurodegenerative Pathologies and Tumour Treatment

Patents

IP Status

Seeking