Polypharmacology remains to be one of the major challenges in drug development, and it opens novel avenues to rationally design the next generation of more effective but less toxic therapeutic agents.
[6] The use of chemoproteomics offers strategies to develop a more holistic understanding of the proteome-wide range of targets a drug interacts with.
[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 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.