Predicting new molecular targets for known drugs
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Keiser, Michael J, et al. Predicting New Molecular Targets for Known Drugs. 2009. https://doi.org/10.17615/awee-yj58APA
Keiser, M., Setola, V., Irwin, J., Laggner, C., Abbas, A., Hufeisen, S., Jensen, N., Kuijer, M., Matos, R., Tran, T., Whaley, R., Glennon, R., Hert, J., Thomas, K., Edwards, D., Schoichet, B., & Roth, B. (2009). Predicting new molecular targets for known drugs. https://doi.org/10.17615/awee-yj58Chicago
Keiser, Michael J., Vincent Setola, John J Irwin, Christian Laggner, Atheir I Abbas, Sandra J Hufeisen, Niels H Jensen et al. 2009. Predicting New Molecular Targets for Known Drugs. https://doi.org/10.17615/awee-yj58- Creator
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Keiser, Michael J.
- Other Affiliation: Department of Pharmaceutical Chemistry, Graduate Group in Bioinformatics, University of California San Francisco
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Setola, Vincent
- Other Affiliation: NIMH Psychoactive Drug Screening Program, Department of Pharmacology, Case Western Reserve University School of Medicine
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Irwin, John J.
- Other Affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco
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Laggner, Christian
- Other Affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco
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Abbas, Atheir I.
- Other Affiliation: Department of Biochemistry, Case Western Reserve University School of Medicine
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Hufeisen, Sandra J.
- Affiliation: Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry
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Jensen, Niels H.
- Affiliation: Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry
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Kuijer, Michael B.
- Other Affiliation: NIMH Psychoactive Drug Screening Program, Department of Pharmacology, Case Western Reserve University School of Medicine
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Matos, Roberto C.
- Other Affiliation: NIMH Psychoactive Drug Screening Program, Department of Pharmacology, Case Western Reserve University School of Medicine
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Tran, Thuy B.
- Other Affiliation: NIMH Psychoactive Drug Screening Program, Department of Pharmacology, Case Western Reserve University School of Medicine
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Whaley, Ryan
- Other Affiliation: NIMH Psychoactive Drug Screening Program, Department of Pharmacology, Case Western Reserve University School of Medicine
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Glennon, Richard A.
- Other Affiliation: Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University
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Hert, Jerome
- Other Affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco
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Thomas, Kelan L.H.
- Other Affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco
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Edwards, Douglas D.
- Other Affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco
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Schoichet, Brian K.
- Other Affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco
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Roth, Bryan
- ORCID: https://orcid.org/0000-0002-0561-6534
- Affiliation: Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry
- Other Affiliation: NIMH Psychoactive Drug Screening Program, Case Western Reserve University School of Medicine
- Abstract
- Although drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug–target combinations exist, it would be useful to explore possible interactions computationally. Here we compared 3,665 US Food and Drug Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested experimentally, including the antagonism of the β1 receptor by the transporter inhibitor Prozac, the inhibition of the 5-hydroxytryptamine (5-HT) transporter by the ion channel drug Vadilex, and antagonism of the histamine H4 receptor by the enzyme inhibitor Rescriptor. Overall, 23 new drug–target associations were confirmed, five of which were potent (less than 100 nM). The physiological relevance of one, the drug N,N-dimethyltryptamine (DMT) on serotonergic receptors, was confirmed in a knockout mouse. The chemical similarity approach is systematic and comprehensive, and may suggest side-effects and new indications for many drugs.
- Date of publication
- 2009
- DOI
- Identifier
- 2-s2.0-70449634957
- https://doi.org/10.1038/nature08506
- Related resource URL
- Resource type
- Article
- Rights statement
- In Copyright
- Journal title
- Nature
- Journal volume
- 462
- Journal issue
- 7270
- Page start
- 175
- Page end
- 181
- Language
- English
- Version
- Postprint
- ISSN
- 1476-4687
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