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Pharmaceutical Research

, Volume 28, Issue 8, pp 1785–1791 | Cite as

Finding Promiscuous Old Drugs for New Uses

  • Sean Ekins
  • Antony J. Williams
Perspectives

ABSTRACT

From research published in the last six years we have identified 34 studies that have screened libraries of FDA-approved drugs against various whole cell or target assays. These studies have each identified one or more compounds with a suggested new bioactivity that had not been described previously. We now show that 13 of these drugs were active against more than one additional disease, thereby suggesting a degree of promiscuity. We also show that following compilation of all the studies, 109 molecules were identified by screening in vitro. These molecules appear to be statistically more hydrophobic with a higher molecular weight and AlogP than orphan-designated products with at least one marketing approval for a common disease indication or one marketing approval for a rare disease from the FDA’s rare disease research database. Capturing these in vitro data on old drugs for new uses will be important for potential reuse and analysis by others to repurpose or reposition these or other existing drugs. We have created databases which can be searched by the public and envisage that these can be updated as more studies are published.

KEY WORDS

cheminformatics HTS old drugs repositioning repurposing 

Notes

ACKNOWLEDGMENTS and DISCLOSURES

SE gratefully acknowledges David Sullivan (Johns Hopkins University) for discussing and suggesting references for JHCCL. Accelrys are kindly thanked for providing Discovery Studio.

SE consults for Collaborative Drug Discovery, Inc. on a Bill and Melinda Gates Foundation: Grant#49852 “Collaborative drug discovery for TB through a novel database of SAR data optimized to promote data archiving and sharing.”

Supplementary material

11095_2011_486_MOESM1_ESM.doc (198 kb)
Supplemental Table I Drugs identified with new uses using HTS methods. This table greatly extends a previously published version (1). CCR5, Chemokine receptor 5; DHFR, Dihydrofolate reductase; DOA, Drugs of abuse, FDA, Food and Drug Administration; GLT1, Glutamate transporter 1; HSP-90, Heat shock protein 90; JHCCL, John Hopkins Clinical Compound Library; Mtb, Mycobacterium tuberculosis; NK-1, neurokinin- 1 receptor; OCTN2 (DOC 197 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Collaborations in ChemistryJenkintownUSA
  2. 2.Collaborative Drug DiscoveryBurlingameUSA
  3. 3.Department of Pharmaceutical SciencesUniversity of MarylandBaltimoreUSA
  4. 4.Department of PharmacologyUniversity of Medicine & Dentistry of New Jersey (UMDNJ) Robert Wood Johnson Medical SchoolPiscatawayUSA
  5. 5.Royal Society of ChemistryWake ForestUSA

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