Literature DB >> 21607776

Finding promiscuous old drugs for new uses.

Sean Ekins1, Antony J Williams.   

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.

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Year:  2011        PMID: 21607776     DOI: 10.1007/s11095-011-0486-6

Source DB:  PubMed          Journal:  Pharm Res        ISSN: 0724-8741            Impact factor:   4.200


  38 in total

1.  Drug screening to identify suppressors of GFAP expression.

Authors:  Woosung Cho; Michael Brenner; Noel Peters; Albee Messing
Journal:  Hum Mol Genet       Date:  2010-06-10       Impact factor: 6.150

2.  Characteristic physical properties and structural fragments of marketed oral drugs.

Authors:  Michal Vieth; Miles G Siegel; Richard E Higgs; Ian A Watson; Daniel H Robertson; Kenneth A Savin; Gregory L Durst; Philip A Hipskind
Journal:  J Med Chem       Date:  2004-01-01       Impact factor: 7.446

Review 3.  Finding new tricks for old drugs: an efficient route for public-sector drug discovery.

Authors:  Kerry A O'Connor; Bryan L Roth
Journal:  Nat Rev Drug Discov       Date:  2005-12       Impact factor: 84.694

4.  Modeling promiscuity based on in vitro safety pharmacology profiling data.

Authors:  Kamal Azzaoui; Jacques Hamon; Bernard Faller; Steven Whitebread; Edgar Jacoby; Andreas Bender; Jeremy L Jenkins; Laszlo Urban
Journal:  ChemMedChem       Date:  2007-06       Impact factor: 3.466

Review 5.  Novel web-based tools combining chemistry informatics, biology and social networks for drug discovery.

Authors:  Moses Hohman; Kellan Gregory; Kelly Chibale; Peter J Smith; Sean Ekins; Barry Bunin
Journal:  Drug Discov Today       Date:  2009-02-11       Impact factor: 7.851

6.  Novel chemical space exploration via natural products.

Authors:  Josefin Rosén; Johan Gottfries; Sorel Muresan; Anders Backlund; Tudor I Oprea
Journal:  J Med Chem       Date:  2009-04-09       Impact factor: 7.446

7.  Discovery of trypanocidal compounds by whole cell HTS of Trypanosoma brucei.

Authors:  Zachary B Mackey; Arthur M Baca; Jeremy P Mallari; Beth Apsel; Anang Shelat; Elizabeth J Hansell; Peter K Chiang; Brian Wolff; Kiplin R Guy; Janice Williams; James H McKerrow
Journal:  Chem Biol Drug Des       Date:  2006-05       Impact factor: 2.817

8.  A collaborative database and computational models for tuberculosis drug discovery.

Authors:  Sean Ekins; Justin Bradford; Krishna Dole; Anna Spektor; Kellan Gregory; David Blondeau; Moses Hohman; Barry A Bunin
Journal:  Mol Biosyst       Date:  2010-02-09

9.  New anti-tuberculosis agents amongst known drugs.

Authors:  Kathryn E A Lougheed; Debra L Taylor; Simon A Osborne; Justin S Bryans; Roger S Buxton
Journal:  Tuberculosis (Edinb)       Date:  2009-08-20       Impact factor: 3.131

10.  Computational models for drug inhibition of the human apical sodium-dependent bile acid transporter.

Authors:  Xiaowan Zheng; Sean Ekins; Jean-Pierre Raufman; James E Polli
Journal:  Mol Pharm       Date:  2009 Sep-Oct       Impact factor: 4.939

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  19 in total

1.  Screening of novel inhibitors targeting lactate dehydrogenase A via four molecular docking strategies and dynamics simulations.

Authors:  Rong Sun; Xin Li; Yuanyuan Li; Xun Zhang; Xinru Li; Xiaoyu Li; Zheng Shi; Jinku Bao
Journal:  J Mol Model       Date:  2015-05-02       Impact factor: 1.810

2.  Identification of novel activators of constitutive androstane receptor from FDA-approved drugs by integrated computational and biological approaches.

Authors:  Caitlin Lynch; Yongmei Pan; Linhao Li; Stephen S Ferguson; Menghang Xia; Peter W Swaan; Hongbing Wang
Journal:  Pharm Res       Date:  2012-10-23       Impact factor: 4.200

3.  Immunohistochemical Analysis of the Stem Cell Marker LGR5 in Pediatric Liver Disease.

Authors:  Zahida Khan; Anne Orr; George K Michalopoulos; Sarangarajan Ranganathan
Journal:  Pediatr Dev Pathol       Date:  2017 Jan-Feb

Review 4.  World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients.

Authors:  Christina N Kontoghiorghe; Nicholas Andreou; Katerina Constantinou; George J Kontoghiorghes
Journal:  World J Methodol       Date:  2014-09-26

5.  A substrate pharmacophore for the human organic cation/carnitine transporter identifies compounds associated with rhabdomyolysis.

Authors:  Sean Ekins; Lei Diao; James E Polli
Journal:  Mol Pharm       Date:  2012-02-28       Impact factor: 4.939

Review 6.  Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma.

Authors:  Eleanor M Pritchard; Michael A Dyer; R Kiplin Guy
Journal:  Mini Rev Med Chem       Date:  2016       Impact factor: 3.862

7.  Identification of Nitazoxanide as a Group I Metabotropic Glutamate Receptor Negative Modulator for the Treatment of Neuropathic Pain: An In Silico Drug Repositioning Study.

Authors:  Ni Ai; Richard D Wood; William J Welsh
Journal:  Pharm Res       Date:  2015-03-12       Impact factor: 4.200

8.  Isolation and identification of two alkaloid structures with radical scavenging activity from Actinokineospora sp. UTMC 968, a new promising source of alkaloid compounds.

Authors:  Bahareh Heidari; Fatemeh Mohammadipanah
Journal:  Mol Biol Rep       Date:  2018-09-21       Impact factor: 2.316

9.  Collaboration for rare disease drug discovery research.

Authors:  Nadia K Litterman; Michele Rhee; David C Swinney; Sean Ekins
Journal:  F1000Res       Date:  2014-10-31

10.  Enhancing hit identification in Mycobacterium tuberculosis drug discovery using validated dual-event Bayesian models.

Authors:  Sean Ekins; Robert C Reynolds; Scott G Franzblau; Baojie Wan; Joel S Freundlich; Barry A Bunin
Journal:  PLoS One       Date:  2013-05-07       Impact factor: 3.240

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