Implications of Indolethylamine N-Methyltransferase (INMT) in Health and Disease: Biological Functions, Disease Associations, Inhibitors, and Analytical Approaches.

Summary

Indolethylamine N-methyltransferase (INMT) is an enzyme that adds a methyl group to compounds such as tryptamine, serotonin, and dopamine. Dysregulation of INMT activity is linked to neuropsychiatric disorders, neurodegeneration, and several cancers. This review describes the enzyme's structure, its role in disease, and methods to measure its activity, including both radiolabeled and non-radiolabeled assays. It also surveys natural and synthetic inhibitors of INMT that may have therapeutic value. The authors argue that INMT is an underexplored target for drug development and that integrating structural biology, disease pathology, and inhibitor profiling could advance therapeutic applications.

Study at a glance

Abstract

Indolethylamine N-methyltransferase (INMT) is a Class 1 methyltransferase responsible for N-methylation of various endogenous and exogenous compounds, including tryptamine, serotonin, and dopamine. This review aims to provide a comprehensive overview of the biological and therapeutic relevance of INMT, emphasizing the human isoform (hINMT), highlighting its structural characteristics, disease association, and recent advances in analytical strategies. Dysregulation of INMT activity has been linked to a range of pathological conditions, including neuropsychiatric disorders, neurodegeneration, and several forms of cancer. These associations are addressed by integrating current findings across disease pathophysiology, enzyme inhibition, and analytical methodologies, including both radiolabeled and non-radiolabeled in vitro assays, for measuring INMT activity. We further explored the chemical diversity of INMT inhibitors, both natural and synthetic, and highlighted key compounds with therapeutic relevance. Additionally, recent commercial assays for quantifying INMT activity are emphasized. By integrating emerging evidence from structural biology and disease pathology with inhibitor profiling and analytical technologies, this review highlights the underexplored therapeutic potential of targeting INMT and underscores its value as a promising target for drug development and therapeutic applications.