[Multi-targeting drugs: past, present and future].

The one disease - one target - one drug paradigm was an almost dominant principle in drug discovery from the 1960s to the 2000s. The stagnation and even decline in the productivity of drug innovation around the turn of the millennium and beyond, the realization of limitations of the one-target approach, especially in the treatment of multifactorial diseases, have drawn attention considerably to the one disease - multiple target - one drug multi-targeting drug concept. In this review, we outline old and new molecular design strategies and their practical implementation with own and other examples that also demonstrate unique therapeutic and diagnostic values and benefits of the multi-targeting approach. Finally, we point out that the full potential of the multi-targeting concept can emerge through data analytics and association methods (such as artificial intelligence) and system-based approach, preferably by linking it to quantitative systems pharmacology. This new systems pharmacology drug approach may also lead to novel breakthrough drugs, drug combinations and drug repositioning. Orv Hetil. 2020; 161(14): 523-531.