Core Insights - The recent failure of Janux's drug candidate has cast a shadow over the future of prodrugs, which are compounds that are inactive until metabolized in the body to release active drugs [1] - Despite setbacks, prodrugs remain crucial in addressing challenges in drug development, such as poor solubility, low stability, insufficient targeting, and significant side effects [1] Group 1: Prodrug Mechanism and Classification - Prodrugs can be categorized into three main types: bioprecursor prodrugs, carrier prodrugs, and synergistic prodrugs, each utilizing different activation mechanisms [2] - According to statistics from "Nature Drug Discovery," the FDA has approved 178 prodrugs, representing 9% of all approved small molecule drugs, with the largest indications being anti-infectives (33%) and chemotherapy agents (18%) [2] Group 2: Advantages and Applications of Prodrugs - Prodrugs enhance drug solubility, membrane permeability, and stability, allowing previously unviable compounds to reach clinical application, as seen with Sofosbuvir and Aspirin [5] - The PROTAC technology, once seen as revolutionary, faces challenges in pharmacokinetics, but recent studies suggest prodrug strategies could improve its viability [5] Group 3: Evolution of Prodrug Technology - Prodrug technology has evolved through three generations, from simple chemical modifications to AI-driven precise designs that enhance efficacy and safety [7][8] - The third generation focuses on microenvironment-triggered prodrugs, which utilize specific enzymes or conditions in disease tissues for targeted activation [8] Group 4: Market Trends and Future Prospects - The global prodrug market is projected to grow from under $20 billion in 2015 to approximately $35 billion by 2025, with a stable annual growth rate of around 6% [10] - Prodrugs are increasingly seen as a key driver of innovation in high-risk therapeutic areas like oncology and central nervous system disorders, attracting significant investment [10] Group 5: Challenges and Innovations - Future development of prodrugs faces challenges such as individual metabolic variability and the heterogeneity of tumor microenvironments, which can affect drug activation and efficacy [13] - Companies like Gilead and domestic firms are actively pursuing innovative prodrug platforms, with notable advancements in various therapeutic areas [14][15]