title: Novel Phenotypic Outcomes Identified for a Public Collection of Approved Drugs from a Publicly Accessible Panel of Assays.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Shinn
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Jaken
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Oliver
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Francis S
authors.initials: FS
authors.lastname: Willard
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Heidler
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Peery
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Oler
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Shaoyou
authors.initials: S
authors.lastname: Chu
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Noel
authors.initials: N
authors.lastname: Southall
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Dexheimer
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Smallwood
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Ruili
authors.initials: R
authors.lastname: Huang
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Guha
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Ajit
authors.initials: A
authors.lastname: Jadhav
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: Cox
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Austin
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Anton
authors.initials: A
authors.lastname: Simeonov
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: G Sitta
authors.initials: GS
authors.lastname: Sittampalam
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Saba
authors.initials: S
authors.lastname: Husain
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Natalie
authors.initials: N
authors.lastname: Franklin
authors.affiliation: Indiana University School of Informatics and Computing, Bloomington, Indiana, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wild
authors.affiliation: Indiana University School of Informatics and Computing, Bloomington, Indiana, United States of America.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Sutherland
authors.affiliation: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Thomas
mesh_terms: D045744:Cell Line, Tumor; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D058492:Drug Repositioning; D057166:High-Throughput Screening Assays; D006801:Humans; D020128:Inhibitory Concentration 50; D010641:Phenotype; D054852:Small Molecule Libraries / Q000494:pharmacology
chemical_list: D054852:Small Molecule Libraries