An Overview of ADAR Inhibitors: Mechanisms, Applications, and Future Directions

Abstract

Adenosine deaminases acting on RNA (ADARs) are enzymes responsible for converting adenosine to inosine in double-stranded RNA through a process known as A-to-I editing. This modification is essential for regulating RNA function, impacting key processes such as immune response, gene expression, and RNA stability. ADARs, especially ADAR1, have been linked to several diseases, including cancer, viral infections, and autoimmune disorders, making them promising targets for therapeutic development. Currently, no FDA-approved drugs are specifically marketed as ADAR inhibitors. This review offers a brief analysis of known ADAR inhibitors, with a focus on their mechanisms of action, structural properties, and potential applications. We explore a range of inhibitors, including small molecules, peptide-based inhibitors, natural compounds, and RNA-based inhibitors, and discuss their ability to selectively modulate ADAR activity. The review also addresses the therapeutic implications of these inhibitors in cancer, viral infections, and inflammatory diseases. In addition, we examine future directions for developing more selective and potent ADAR inhibitors, emphasizing both the challenges and opportunities in the field. By consolidating current findings and identifying existing gaps, this review aims to enhance the understanding and therapeutic potential of ADAR inhibition.