Clinical Investigation of Tyrosinase Inhibitors: Past, Present, and Future

ABSTRACT Tyrosinase (EC 1.14.18.1) is a pivotal enzyme that catalyzes the conversion of L‐tyrosine to dopaquinone through a dual oxidation process, initiating melanin biosynthesis. Melanin plays a critical role in various biological processes, and its overproduction is associated with multiple conditions. Tyrosinase plays a crucial role in immune regulation by regulating the activity of immune cells and enhancing the immune response of the body. It is essential for maintaining skin health and preventing autoimmune diseases. In addition, tyrosinase has shown potential in immunotherapy, especially in the treatment of malignant melanoma and autoimmune diseases such as vitiligo. Inhibiting tyrosinase to reduce melanin synthesis has emerged as a promising therapeutic strategy with applications in skin whitening, melasma treatment, acne management, Parkinson's disease (PD) intervention, melanoma prevention, and overcoming immunotherapy resistance. By leveraging the tyrosinase‐related comprehensive data documented in the BRENDA database, we have systematically summarized the effective information, including its classification, structural characteristics, catalytic functions, biosynthesis pathways, substrate specificity profiles, reaction products, and associated disease mechanisms, and so forth. This review comprehensively examines the therapeutic mechanisms, development history, and current clinical status of tyrosinase inhibitors at preclinical and advanced stages. We highlight recent research progress, focusing on evidence from animal models, preclinical studies, and human clinical trials across different indications. Additionally, we critically analyze the challenges and limitations in the field and provide insights into future directions for optimizing tyrosinase inhibitors. By synthesizing current knowledge and advancements, this review aims to underscore the therapeutic potential of tyrosinase inhibition and its role in addressing diverse medical needs.