Muhammad Rafehi, Marius Möller, Wouroud Ismail Al-Khalil, Sven Marcel Stefan
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Medicinal Polypharmacology in the Clinic - Translating the Polypharmacolome into Therapeutic Benefit.
Drugs with multiple targets, often annotated as 'unselective', 'promiscuous', 'multitarget', or 'polypharmacological', are widely considered in both academic and industrial research as a high risk due to the likelihood of adverse effects. However, retrospective analyses have shown that particularly approved drugs bear rich polypharmacological profiles. This raises the question whether our perception of the specificity paradigm ('one drug-one target concept') is correct - and if specifically multitarget drugs should be developed instead of being rejected. These questions provoke a paradigm shift - regarding the development of polypharmacological drugs not as a 'waste of investment', but acknowledging the existence of a 'lack of investment'. This perspective provides an insight into modern drug development highlighting latest drug candidates that have not been assessed in a broader polypharmacology-based context elsewhere embedded in a historic framework of classical and modern approved multitarget drugs. The article shall be an inspiration to the scientific community to re-consider current standards, and more, to evolve to a better understanding of polypharmacology from a challenge to an opportunity.
期刊介绍:
Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to:
-(pre)formulation engineering and processing-
computational biopharmaceutics-
drug delivery and targeting-
molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)-
pharmacokinetics, pharmacodynamics and pharmacogenetics.
Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.