Polypharmacology across multiple proteins

Polypharmacology across multiple proteins refers to the phenomenon or therapeutic strategy where a single drug molecule interacts with multiple distinct biological targets (Nature Reviews Drug Discovery, 2019). Unlike the traditional "one drug, one target" paradigm, polypharmacology recognizes that many effective drugs exert their clinical benefits by modulating complex signaling networks rather than a single protein (PubMed, PMID: 22873433). This approach is particularly relevant in treating multifactorial diseases such as cancer, psychiatric disorders, and neurodegenerative conditions, where hitting a single target may be insufficient due to biological redundancy or compensatory pathways (NIH, 2021). While polypharmacology can enhance efficacy and overcome drug resistance, it also poses challenges in drug design, as it increases the risk of off-target effects and unpredictable toxicities (Pharmacological Reviews, 2013). Modern drug discovery often employs computational modeling and network pharmacology to intentionally design "multi-target ligands" that hit a specific profile of targets to optimize the therapeutic index (Briefings in Bioinformatics, 2017). This strategy is exemplified by drugs like clozapine, which interacts with numerous G protein-coupled receptors to treat schizophrenia, and multi-kinase inhibitors used in oncology (StatPearls, 2023). The shift towards polypharmacology represents a move from reductionist biology to a systems-level understanding of drug-host interactions (Wikipedia, 2024).

Other names

Multi-target pharmacologyNetwork pharmacologyDrug promiscuityMulti-target drug ligands

Simultaneous modulation of multiple distinct molecular targets (e.g., receptors, enzymes, transporters) to achieve a synergistic therapeutic effect or manage complex disease networks (Nature Reviews Drug Discovery, 2019).