Publication:
Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond

Issued Date

2016-07-01

Resource Type

Article

ISSN

15537374
15537366

DOI

10.1371/journal.ppat.1005763

Other identifier(s)

2-s2.0-84982980463

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS Pathogens. Vol.12, No.7 (2016)

Suggested Citation

Wesley C. Van Voorhis, John H. Adams, Roberto Adelfio, Vida Ahyong, Myles H. Akabas, Pietro Alano, Aintzane Alday, Yesmalie Alemán Resto, Aishah Alsibaee, Ainhoa Alzualde, Katherine T. Andrews, Simon V. Avery, Vicky M. Avery, Lawrence Ayong, Mark Baker, Stephen Baker, Choukri Ben Mamoun, Sangeeta Bhatia, Quentin Bickle, Lotfi Bounaadja, Tana Bowling, Jürgen Bosch, Lauren E. Boucher, Fabrice F. Boyom, Jose Brea, Marian Brennan, Audrey Burton, Conor R. Caffrey, Grazia Camarda, Manuela Carrasquilla, Dee Carter, Maria Belen Cassera, Ken Chih-Chien Cheng, Worathad Chindaudomsate, Anthony Chubb, Beatrice L. Colon, Daisy D. Colón-López, Yolanda Corbett, Gregory J. Crowther, Noemi Cowan, Sarah D’Alessandro, Na Le Dang, Michael Delves, Joseph L. DeRisi, Alan Y. Du, Sandra Duffy, Shimaa Abd El-Salam El-Sayed, Michael T. Ferdig, José A. Fernández Robledo, David A. Fidock, Isabelle Florent, Patrick V.T. Fokou, Ani Galstian, Francisco Javier Gamo, Suzanne Gokool, Ben Gold, Todd Golub, Gregory M. Goldgof, Rajarshi Guha, W. Armand Guiguemde, Nil Gural, R. Kiplin Guy, Michael A.E. Hansen, Kirsten K. Hanson, Andrew Hemphill, Rob Hooft van Huijsduijnen, Takaaki Horii, Paul Horrocks, Tyler B. Hughes, Christopher Huston, Ikuo Igarashi, Katrin Ingram-Sieber, Maurice A. Itoe, Ajit Jadhav, Amornrat Naranuntarat Jensen, Laran T. Jensen, Rays H.Y. Jiang, Annette Kaiser, Jennifer Keiser, Thomas Ketas, Sebastien Kicka, Sunyoung Kim, Kiaran Kirk, Vidya P. Kumar, Dennis E. Kyle, Maria Jose Lafuente, Scott Landfear, Nathan Lee, Sukjun Lee, Adele M. Lehane Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond. PLoS Pathogens. Vol.12, No.7 (2016). doi:10.1371/journal.ppat.1005763 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/43004

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Organizational Units

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Title

Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond

Author(s)

Wesley C. Van Voorhis
 John H. Adams
 Roberto Adelfio
 Vida Ahyong
 Myles H. Akabas
 Pietro Alano
 Aintzane Alday
 Yesmalie Alemán Resto
 Aishah Alsibaee
 Ainhoa Alzualde
 Katherine T. Andrews
 Simon V. Avery
 Vicky M. Avery
 Lawrence Ayong
 Mark Baker
 Stephen Baker
 Choukri Ben Mamoun
 Sangeeta Bhatia
 Quentin Bickle
 Lotfi Bounaadja
 Tana Bowling
 Jürgen Bosch
 Lauren E. Boucher
 Fabrice F. Boyom
 Jose Brea
 Marian Brennan
 Audrey Burton
 Conor R. Caffrey
 Grazia Camarda
 Manuela Carrasquilla
 Dee Carter
 Maria Belen Cassera
 Ken Chih-Chien Cheng
 Worathad Chindaudomsate
 Anthony Chubb
 Beatrice L. Colon
 Daisy D. Colón-López
 Yolanda Corbett
 Gregory J. Crowther
 Noemi Cowan
 Sarah D’Alessandro
 Na Le Dang
 Michael Delves
 Joseph L. DeRisi
 Alan Y. Du
 Sandra Duffy
 Shimaa Abd El-Salam El-Sayed
 Michael T. Ferdig
 José A. Fernández Robledo
 David A. Fidock
 Isabelle Florent
 Patrick V.T. Fokou
 Ani Galstian
 Francisco Javier Gamo
 Suzanne Gokool
 Ben Gold
 Todd Golub
 Gregory M. Goldgof
 Rajarshi Guha
 W. Armand Guiguemde
 Nil Gural
 R. Kiplin Guy
 Michael A.E. Hansen
 Kirsten K. Hanson
 Andrew Hemphill
 Rob Hooft van Huijsduijnen
 Takaaki Horii
 Paul Horrocks
 Tyler B. Hughes
 Christopher Huston
 Ikuo Igarashi
 Katrin Ingram-Sieber
 Maurice A. Itoe
 Ajit Jadhav
 Amornrat Naranuntarat Jensen
 Laran T. Jensen
 Rays H.Y. Jiang
 Annette Kaiser
 Jennifer Keiser
 Thomas Ketas
 Sebastien Kicka
 Sunyoung Kim
 Kiaran Kirk
 Vidya P. Kumar
 Dennis E. Kyle
 Maria Jose Lafuente
 Scott Landfear
 Nathan Lee
 Sukjun Lee
 Adele M. Lehane

Other Contributor(s)

University of Washington, Seattle
 University of South Florida, Tampa
 Swiss Tropical and Public Health Institute (Swiss TPH)
 Universitat Basel
 University of California, San Francisco
 Albert Einstein College of Medicine of Yeshiva University
 Istituto Superiore Di Sanita
 Biobide
 Bigelow Laboratory for Ocean Sciences
 Royal College of Surgeons in Ireland
 Griffith University
 QIMR Berghofer Medical Research Institute
 University of Nottingham
 Institut Pasteur Korea
 Clinical Pharmacology and Nephrology
 UCL
 Nuffield Department of Clinical Medicine
 London School of Hygiene & Tropical Medicine
 Yale University
 Massachusetts Institute of Technology
 Museum National d'Histoire Naturelle
 Scynexis, Inc.
 Johns Hopkins Bloomberg School of Public Health
 Universite de Yaounde I
 Universidad de Santiago de Compostela
 Pennsylvania State University
 The University of Sydney
 Virginia Polytechnic Institute and State University
 National Center for Advancing Translational Sciences
 Mahidol University
 University of South Florida, Morsani College of Medicine
 Università degli Studi di Milano
 Washington University in St. Louis
 Imperial College London
 University of California, San Diego
 Obihiro University of Agriculture and Veterinary Medicine
 Mansoura University
 University of Notre Dame
 Columbia University Medical Center
 Broad Institute
 GlaxoSmithKline plc, Spain
 Northwick Park Hospital
 Weill Cornell Medical College
 St. Jude Children's Research Hospital
 University of Texas at San Antonio
 University of Lisbon Faculty of Medicine, Institute of Molecular Medicine
 University of Bern
 Medicines for Malaria Venture
 Eisai Co., Ltd.
 Keele University
 University of Vermont College of Medicine
 Institute of Pharmacogenetics
 Université de Genève
 LSU Health Sciences Center - New Orleans
 Research School of Biologyn National University
 Oregon Health and Science University
 Monash University
 Universiteit Antwerpen
 The Council for Scientific and Industrial Research
 Wellcome Trust Sanger Institute

Abstract

© 2016 Public Library of Science. All rights reserved. A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Immunology and Microbiology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/43004

Collections

Scopus 2016-2017