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

Abstract

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.