Review on the application of metalloporphyrin catalysts as cytochrome P450 enzyme mimics in biomimetic modeling

Drug research, particularly in the early discovery phase, increasingly seeks cost-effective and reliable <i>in vitro</i> models to predict drug metabolism. Metalloporphyrins (MPs), due to their structural and functional resemblance to the heme group of cytochrome P450 enzymes (CYP450s), have emerged as versatile biomimetic catalysts for oxidative reactions. This review focuses specifically on metalloporphyrin-based biomimetic catalysis for oxidative drug metabolism studied in scientific papers publishedin the last 10 years (2015-2025). Unlike previous reviews, we highlight the comparative advantages and limitations of MP systems versus enzymatic models (microsomes, recombinant CYP450s), including aspects of selectivity, functional group tolerance, and scalability. We further discuss recent innovations in immobilization strategies, nanostructured supports, and continuous-flow applications that expand MPs' utility in drug metabolism studies. While challenges remain, particularly regioselectivity and oxidation of unactivated C-H bonds, we conclude that MPs serve as complementary tools for metabolite synthesis and mechanistic investigations, and their integration with modern microreactors and peptide-based designs holds promise for future biomimetic drug metabolism research.