CYP2E1 as an Emerging Drug Target for Inflammatory Diseases: Roles, Therapeutic Potential, and Inhibitor Development

Inflammation plays a central role in the development of many diseases. However, the existing anti-inflammatory drugs exhibit limited clinical efficacy in specific disease settings, highlighting the urgent need to identify novel therapeutic targets. Cytochrome P450 2E1 (CYP2E1) is a key metabolic enzyme that generates ROS as byproducts during its metabolism, thereby promoting oxidative stress and triggering inflammatory responses. Emerging evidence has positioned CYP2E1 as a novel inflammatory target, with the recently developed CYP2E1 inhibitor Q11 demonstrating preclinical therapeutic efficacy across a range of inflammatory conditions, including sepsis, rheumatoid arthritis, neuroinflammation, hepatic inflammation, and several cancers. This review summarizes current advances in understanding the role of CYP2E1 in inflammatory disease pathogenesis and evaluates its target tractability from four perspectives: its association with inflammatory diseases, therapeutic effectiveness, safety profile, and druggability. We further discuss the limitations of existing CYP2E1 inhibitors and the key challenges that need to be addressed to advance their clinical translation. Collectively, this review provides a comprehensive overview for the future development of promising CYP2E1-targeted therapeutic strategies for inflammatory diseases.