Key Points
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The empirical, de novo discovery of multicomponent syncretic drugs requires an integrated informatics and experimental pipeline approach that is dedicated to such a process. Such a method can be used to screen millions of combinations of already approved drugs (or new chemicl entities) for activities in new disease indications55. Scientists at CombinatoRx, Inc. have used this approach to discover numerous syncretic drug candidates that are being tested in early clinical trials (Fig. 5). Such efforts necessarily encompass cross-disciplinary expertise, including mathematics, statistics, physics, chemistry, biology and computer science. With such groups, it is possible to find novel and effective syncretic drugs for a variety of human diseases. Indeed, the systems-based discovery of therapeutics probably represents the next frontier in drug discovery research.
Abstract
Therapeutic regimens that comprise more than one active ingredient are commonly used in clinical medicine. Despite this, most drug discovery efforts search for drugs that are composed of a single chemical entity. A focus in the early drug discovery process on identifying and optimizing the activity of combinations of molecules can result in the identification of more effective drug regimens. A systems perspective facilitates an understanding of the mechanism of action of such drug combinations.
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Acknowledgements
We thank M. Foley for assistance in developing the concepts described here, and J. Lehár, T. Ideker and D. Grau for critical suggestions on this manuscript. B.R.S. is supported in part by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund.
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The authors are employed by, and have equity interests in, CombinatoRx, Inc., a business whose goal is to identify and commercialize novel drug combinations using a systems-based approach.
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Keith, C., Borisy, A. & Stockwell, B. Multicomponent therapeutics for networked systems. Nat Rev Drug Discov 4, 71–78 (2005). https://doi.org/10.1038/nrd1609
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DOI: https://doi.org/10.1038/nrd1609
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