Polypharmacology: new drugs in 2023-2024.

Polypharmacology is an emerging approach to drug design and development that involves the use of multi-target-directed ligands (MTDLs), agents capable of interacting with multiple biological targets simultaneously. The effective treatment of chronic and multifactorial conditions, driven by the dysregulation of multiple interconnected pathways, such as cancer, autoimmune and metabolic disorders, cardiovascular and neurodegenerative diseases, is one of the most substantial challenges in contemporary pharmacology. 'Traditional' single-target-based treatment frequently shows limited effectiveness, as resistance to therapy develops or relapses occur. The rational use of MTDLs seems therefore a promising way to address the complexity of biological systems, feedback mechanisms, crosstalk, and molecular pathways. Many MTDLs have been successfully marketed to date. Moreover, plenty of them offer an additional benefit in comparison to 'traditional' treatment approaches. To assess whether the polypharmacological trend remains prevalent, we thoroughly analysed drugs approved in the years of 2023-2024 in Germany. Among 73 newly introduced substances, 18 are in line with the polypharmacology concept, including 10 antitumor agents, 5 drugs indicated for autoimmune disorders, 1 indicated for hand eczema, 1 antidiabetic (and anti-obesity) drug, and 1 modified corticosteroid.