Drug repurposing through nonhypothesis driven phenotypic screening

The tremendous biological complexity associated with living systems results in significant limitations on the reductionist or target-based drug discovery approach. Increasingly it is being recognized that allowing for more serendipity to enter drug discovery vis-a-vis phenotypic screening provides for more cost-effective drug discovery with higher productivity. Several compelling studies and examples help establish this point of view.

[1]  B. Munos Lessons from 60 years of pharmaceutical innovation , 2009, Nature Reviews Drug Discovery.

[2]  M. V. Regenmortel,et al.  Reductionism and complexity in molecular biology , 2004, HIV/AIDS: Immunochemistry, Reductionism and Vaccine Design.

[3]  Michael Williams,et al.  Productivity Shortfalls in Drug Discovery: Contributions from the Preclinical Sciences? , 2011, Journal of Pharmacology and Experimental Therapeutics.

[4]  R. Stafford,et al.  Off-label prescribing among office-based physicians. , 2006, Archives of internal medicine.

[5]  J. Clader The discovery of ezetimibe: a view from outside the receptor. , 2004, Journal of medicinal chemistry.

[6]  Marc K Hellerstein,et al.  Exploiting Complexity and the Robustness of Network Architecture for Drug Discovery , 2008, Journal of Pharmacology and Experimental Therapeutics.

[7]  M. Williams,et al.  Challenges in the Search for Drugs to Treat Central Nervous System Disorders , 2009, Journal of Pharmacology and Experimental Therapeutics.

[8]  Jun O. Liu,et al.  A clinical drug library screen identifies astemizole as an antimalarial agent , 2006, Nature chemical biology.

[9]  Jun O. Liu,et al.  Inhibitors of Plasmodium falciparum methionine aminopeptidase 1b possess antimalarial activity , 2006, Proceedings of the National Academy of Sciences.

[10]  Marc K Hellerstein,et al.  A critique of the molecular target-based drug discovery paradigm based on principles of metabolic control: advantages of pathway-based discovery. , 2008, Metabolic engineering.

[11]  T. Ashburn,et al.  Drug repositioning: identifying and developing new uses for existing drugs , 2004, Nature Reviews Drug Discovery.

[12]  D. Swinney,et al.  How were new medicines discovered? , 2011, Nature Reviews Drug Discovery.

[13]  F. Rambert,et al.  Central alpha 1-adrenergic stimulation in relation to the behaviour stimulating effect of modafinil; studies with experimental animals. , 1990, European journal of pharmacology.

[14]  C. Stief,et al.  Penile erection and cardiac risk: pathophysiologic and pharmacologic mechanisms. , 2000, The American journal of cardiology.