Systems Biology: Exploring Adverse Drug Reactions (ADRs) Space of Drug Candidates
Pharmaceutical companies are facing ultimate challenge to increase efficiency of drug discovery pipeline to keep up with market demands. Failure of clinical candidates as well as withdrawal of approved and marketed drugs due the undesired effects , or so-called adverse drug reactions (ADRs)- are forcing companies to look on where they can fill the gap. A recent paper in Journal of Chemical Information and Modeling suggests that by analyzing a set of compounds that share a common toxic phenotype and by comparing the pathways they affect with pathways modulated by nontoxic compounds we can establish links between pathways and particular adverse effects. Proposed systems chemical biology approach can predict ADRs those are linked to multiple off-target effects.
Using specific example of Cerivastatin, which was withdrawn from market in 2001 citing the drug-induced rhabdomyolysis, Scheiber et al. demonstate that how drug interfering with cAMP signaling can cause rhabdomyolysis. It appears that in most of cases, where either a drug candidate was failed in advance clinical stage or a drug was called back from market- it was truly possible to predict on- and off-target side effects in early stage itself using existing and avilable informations. Present study make a strong case for the system biology based drug discovery, which can fundamentally change the success rate in clinical trials. Considering the fact that clinical trials are expensive and wasteful, systems biology based drug discovery can bring continued innovation and revenue growth.
Reference:
Josef Scheiber, Bin Chen, Mariusz Milik, Sai Chetan K. Sukuru, Andreas Bender, Dmitri Mikhailov, Steven Whitebread, Jacques Hamon, Kamal Azzaoui, Laszlo Urban, Meir Glick, John W. Davies, Jeremy L. Jenkins (2009). Gaining Insight into Off-Target Mediated Effects of Drug Candidates with a Comprehensive Systems Chemical Biology Analysis Journal of Chemical Information and Modeling DOI: 10.1021/ci800344p
2 Responses to “Systems Biology: Exploring Adverse Drug Reactions (ADRs) Space of Drug Candidates”
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Hello OzFebruary 11, 2012 at 5:56 pm -
Good move by Elsevier, but company need more than PR efforts to save it's ground. Why so afraid accepting the new reality, open is future.February 11, 2012 at 3:01 am
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Dear Entrepreneur, CXO of unknown start-up with uncertain business model, be grounded and humble. cheersFebruary 10, 2012 at 2:53 am
Very true, but the biological interaction space is very complex and to make a better understanding about it we need to integrate all available informations at one place, use of workflow technology can facilitate this kind of analysis very easily (as described in paper, they used single pipeline pilot workflow using available node components). what we really need is determination to explore things in deep before we move at next level of drug discovery
I agree with anilbioma, that we need to integrate all available informations at one place, but I think if we take care of ourselves we won’t need any drugs there for we better be able to take care of ourselves a little more.
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