α/β-Hydrolase Domain (ABHD) Inhibitors as New Potential Therapeutic Options against Lipid-Related Diseases

Much of the experimental evidence in the literature has linked altered lipid metabolism to severe diseases such as cancer, obesity, cardiovascular pathologies, diabetes, and neurodegenerative diseases. Therefore, targeting key effectors of the dysregulated lipid metabolism may represent an effective strategy to counteract these pathological conditions. In this context, alpha/beta-hydrolase domain (ABHD) enzymes represent an important and diversified family of proteins, which are involved in the complex environment of lipid signaling, metabolism, and regulation. Moreover, some members of the ABHD family play an important role in the endocannabinoid system, being designated to terminate the signaling of the key endocannabinoid regulator 2-arachidonoylglycerol. This Perspective summarizes the research progress in the development of ABHD inhibitors and modulators: design strategies, structure-activity relationships, action mechanisms, and biological studies of the main ABHD ligands will be highlighted.

Automated summary

The experimental evidence suggests a link between altered lipid metabolism and severe diseases, highlighting the potential of regulating lipid metabolism as an effective strategy against these conditions. ABHD enzymes, a diverse family of proteins, play crucial roles in lipid signaling, metabolism, and regulation, with some members involved in the endocannabinoid system. This Perspective reviews the development of ABHD inhibitors and modulators, emphasizing design strategies, structure-activity relationships, action mechanisms, and biological studies of main ABHD ligands.