Novel Phenotypic Outcomes Identified for a Public Collection of Approved Drugs from a Publicly Accessible Panel of Assays

Phenotypic assays have a proven track record for generating leads that become first-in-class therapies. Whole cell assays that inform on a phenotype or mechanism also possess great potential in drug repositioning studies by illuminating new activities for the existing pharmacopeia. The National Cent...

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Published inPloS one Vol. 10; no. 7; p. e0130796
Main Authors Lee, Jonathan A, Shinn, Paul, Jaken, Susan, Oliver, Sarah, Willard, Francis S, Heidler, Steven, Peery, Robert B, Oler, Jennifer, Chu, Shaoyou, Southall, Noel, Dexheimer, Thomas S, Smallwood, Jeffrey, Huang, Ruili, Guha, Rajarshi, Jadhav, Ajit, Cox, Karen, Austin, Christopher P, Simeonov, Anton, Sittampalam, G Sitta, Husain, Saba, Franklin, Natalie, Wild, David J, Yang, Jeremy J, Sutherland, Jeffrey J, Thomas, Craig J
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 15.07.2015
Public Library of Science (PLoS)
Subjects
Angiogenesis
Angiogenesis inhibitors
Assaying
Atherosclerosis
Cancer therapies
Cell Line, Tumor
Chemistry
Collection
Drug Approval
Drug Evaluation, Preclinical
Drug Repositioning
Drugs
Fatty acids
High-Throughput Screening Assays
Humans
Informatics
Inhibitory Concentration 50
Innovations
Insulin
Kinases
Laboratories
Library collections
Medical screening
Pharmaceutical sciences
Pharmacology
Phenotype
R&D
Research & development
Rotenone
Small Molecule Libraries - pharmacology
Wnt protein
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Summary:Phenotypic assays have a proven track record for generating leads that become first-in-class therapies. Whole cell assays that inform on a phenotype or mechanism also possess great potential in drug repositioning studies by illuminating new activities for the existing pharmacopeia. The National Center for Advancing Translational Sciences (NCATS) pharmaceutical collection (NPC) is the largest reported collection of approved small molecule therapeutics that is available for screening in a high-throughput setting. Via a wide-ranging collaborative effort, this library was analyzed in the Open Innovation Drug Discovery (OIDD) phenotypic assay modules publicly offered by Lilly. The results of these tests are publically available online at www.ncats.nih.gov/expertise/preclinical/pd2 and via the PubChem Database (https://pubchem.ncbi.nlm.nih.gov/) (AID 1117321). Phenotypic outcomes for numerous drugs were confirmed, including sulfonylureas as insulin secretagogues and the anti-angiogenesis actions of multikinase inhibitors sorafenib, axitinib and pazopanib. Several novel outcomes were also noted including the Wnt potentiating activities of rotenone and the antifolate class of drugs, and the anti-angiogenic activity of cetaben.
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Competing Interests: All authors declare that there are no competing interests (financial or non-financial) or financial obligations that would interfere with the full and objective presentation of the research presented in this manuscript through our affiliations with either the National Center for Advancing Translational Sciences, Indiana University School of Informatics and Computing or the Lilly Research Laboratories. Further, none of the author affiliations alter the authors’ ability to adhere to all PLOS ONE policies on sharing data and material.
Conceived and designed the experiments: AS CPA JAL SJ FSW GSS. Performed the experiments: PS S. Husain NF SO S. Heidler RBP JO SC JS KC. Analyzed the data: PS NS TSD RH AJ RG JAL SJ FSW DJW JJY JJS CJT. Wrote the paper: JAL SJ FSW JJS CJT.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0130796