PLoS ONE (Jan 2015)

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

  • Jonathan A Lee,
  • Paul Shinn,
  • Susan Jaken,
  • Sarah Oliver,
  • Francis S Willard,
  • Steven Heidler,
  • Robert B Peery,
  • Jennifer Oler,
  • Shaoyou Chu,
  • Noel Southall,
  • Thomas S Dexheimer,
  • Jeffrey Smallwood,
  • Ruili Huang,
  • Rajarshi Guha,
  • Ajit Jadhav,
  • Karen Cox,
  • Christopher P Austin,
  • Anton Simeonov,
  • G Sitta Sittampalam,
  • Saba Husain,
  • Natalie Franklin,
  • David J Wild,
  • Jeremy J Yang,
  • Jeffrey J Sutherland,
  • Craig J Thomas

DOI
https://doi.org/10.1371/journal.pone.0130796
Journal volume & issue
Vol. 10, no. 7
p. e0130796

Abstract

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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.