Polypharmacology
Polypharmacology is the design or use of pharmaceutical agents that act on multiple targets or disease pathways.[1]
Despite scientific advancements and an increase of global
The primordial idea of polypharmacology was first proposed in 2004 by Bryan Roth.[8] He reasoned that most common central nervous system disorders are polygenic in origin, and attempts to develop more effective treatments for diseases such as schizophrenia and depression by discovering drugs selective for single molecular targets ('magic bullets') have been largely unsuccessful. He therefore proposed a proof of concept that designing selectively non-selective drugs (that is, 'magic shotguns') that interact with several molecular targets will lead to new and more effective medications for a variety of central nervous system disorders. A similar concept was independently proposed in the year of 2006 by Professor Zhiguo Wang[9] who used the term 'single agent–multiple targets' (SAMT) to describe the same principle as 'magic shotguns' and his research team provided the very first experimental evidence for the feasibility, effectiveness and advantages of SAMT, specifically the 'complex decoy oligodeoxynucleotides technology cdODN' attacking multiple target transcription factors, in the treatment of xenograft breast cancer in mice. Subsequently, Wang's team extended the SAMT to designing single agent that can act on multiple miRNAs targeting cancer cells and cardiac pacemaker channel genes and calcium channel genes as a new therapeutic approach.[10][11][12] Wang's work is now categorized as 'Epigenetic Polypharmacology' or 'Targeted Polypharmacology', a branch of Polypharmacology.[13] In 2008, Professor Keven Shokat and his colleagues described a single compound that blocks the proliferation of tumor cells by direct inhibition of oncogenic tyrosine kinases and phosphatidylinositol-3-OH kinases and termed it 'multitargeted drug' along with the concept of 'Polypharmacology'.[14] Since then, Polypharmacology has become a new branch of Pharmacology discipline and research field as well as one of the new direction and strategies for drug development.[15]