Predicting new molecular targets for known drugs

Michael J. Keiser, Vincent Setola, John J. Irwin, Christian Laggner, Atheir I. Abbas, Sandra J. Hufeisen, Niels H. Jensen, Michael B. Kuijer, Roberto C. Matos, Thuy B. Tran, Ryan Whaley, Richard A. Glennon, Jérôme Hert, Kelan L. H. Thomas, Douglas D. Edwards, Brian K. Shoichet () and Bryan L. Roth ()
Additional contact information
Michael J. Keiser: Department of Pharmaceutical Chemistry,
Vincent Setola: NIMH Psychoactive Drug Screening Program
John J. Irwin: Department of Pharmaceutical Chemistry,
Christian Laggner: Department of Pharmaceutical Chemistry,
Atheir I. Abbas: Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
Sandra J. Hufeisen: The University of North Carolina Chapel Hill School of Medicine, Chapel Hill, North Carolina 27759, USA
Niels H. Jensen: The University of North Carolina Chapel Hill School of Medicine, Chapel Hill, North Carolina 27759, USA
Michael B. Kuijer: NIMH Psychoactive Drug Screening Program
Roberto C. Matos: NIMH Psychoactive Drug Screening Program
Thuy B. Tran: NIMH Psychoactive Drug Screening Program
Ryan Whaley: NIMH Psychoactive Drug Screening Program
Richard A. Glennon: School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, 410 North 12th Street, PO Box 980540, Richmond, Virginia 23298-0540, USA
Jérôme Hert: Department of Pharmaceutical Chemistry,
Kelan L. H. Thomas: Department of Pharmaceutical Chemistry,
Douglas D. Edwards: Department of Pharmaceutical Chemistry,
Brian K. Shoichet: Department of Pharmaceutical Chemistry,
Bryan L. Roth: NIMH Psychoactive Drug Screening Program

Nature, 2009, vol. 462, issue 7270, 175-181

Abstract: 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 (

Date: 2009
References: Add references at CitEc
Citations: View citations in EconPapers (8)

Downloads: (external link)
https://www.nature.com/articles/nature08506 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:462:y:2009:i:7270:d:10.1038_nature08506

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature08506

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().