The metal(loid)s’ dilemma. What's the next step for a new era of inorganic molecules in medicine?

In this paper, we critically examine the key challenges associated with the development of inorganic drugs, a field that remains underrepresented despite its significant therapeutic potential. Currently, most clinically approved pharmaceuticals are organic compounds, a trend driven by multiple interconnected factors that have historically limited the adoption and regulatory approval of metal(loid)-based entities. These challenges include issues related to stability, selectivity, pharmacokinetics, and potential toxicity, which require systematic investigation and innovative solutions. Nevertheless, the profound clinical impact of approved inorganic drugs—particularly transition metal(loid)-based agents for both therapeutic and diagnostic applications—is well-established. The success of these compounds underscores the need for expanded research efforts and optimized clinical protocols to fully harness the advantages of metal-based pharmaceuticals. In this context, we explore emerging strategies to overcome current limitations and accelerate the development of next-generation inorganic drugs. These include the rational design of metal-based therapeutics, the integration of advanced metallomics and metalloproteomics, and the application of AI-driven predictive modeling to improve drug selectivity, bioavailability, and safety. By overcoming these challenges through an interdisciplinary approach, metal-based medicine will advance significantly, expanding its impact across a wide range of therapeutic applications.