# Methods for Assessing MAGL Enzymatic Activity: An Extensive Review of Past and Emerging Approaches

## TL;DR

This review summarizes methods to measure MAGL enzyme activity, a potential target for cancer and metabolic disease therapies.

## Contribution

A comprehensive and critical overview of past and emerging MAGL activity assessment methods.

## Key findings

- Multiple biochemical methods exist for measuring MAGL activity, including radiometric and fluorescence-based assays.
- Each method has distinct advantages and limitations, influencing their suitability for different experimental needs.
- The review supports the development of novel MAGL inhibitors for therapeutic applications.

## Abstract

Monoacylglycerol lipase (MAGL) is a key serine hydrolase involved in lipid metabolism, catalyzing the hydrolysis of monoacylglycerols into free fatty acids and glycerol. MAGL plays a central role in regulating endocannabinoid signaling and lipid homeostasis, processes often dysregulated in cancer and other pathological conditions. In recent years, MAGL has emerged as a promising therapeutic target, particularly in oncology, where its inhibition has shown potential to impair tumor growth, metastasis, and inflammation-driven processes. Alongside the development of selective MAGL inhibitors, several biochemical methods have been established to measure MAGL enzymatic activity, providing essential tools for target validation and inhibitor characterization. In this review, we provide a comprehensive and critical overview of the main approaches developed for MAGL activity evaluation, including radiometric, chromatographic, colorimetric, fluorescence-based, bioluminescence-based, and activity-based protein profiling (ABPP) assays. For each method, we discuss principles, advantages, and limitations. This review aims to support researchers in the selection of the most appropriate assay strategy for their experimental needs, ultimately fostering the rapid and accurate development of novel MAGL inhibitors with potential applications in cancer therapy and metabolic disease management.