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

Wesley C. Van Voorhis; John H. Adams; Roberto Adelfio; Vida Ahyong; Myles H. Akabas; Pietro Alano; Aintzane Alday; Yesmalie Aleman 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; Juergen 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. Colon-Lopez; 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; Jose A. Fernandez 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; Fengwu Li; David Little; Liqiong Liu; Manuel Llinas; Maria I. Loza; Aristea Lubar; Leonardo Lucantoni; Isabelle Lucet; Louis Maes; Dalu Mancama; Nuha R. Mansour; Sandra March; Sheena McGowan; Iset Medina Vera; Stephan Meister; Luke Mercer; Jordi Mestres; Alvine N. Mfopa; Raj N. Misra; Seunghyun Moon; John P. Moore; Francielly Morais Rodrigues da Costa; Joachim Mueller; Arantza Muriana; Stephen Nakazawa Hewitt; Bakela Nare; Carl Nathan; Nathalie Narraidoo; Sujeevi Nawaratna; Kayode K. Ojo; Diana Ortiz; Gordana Panic; George Papadatos; Silvia Parapini; Kailash Patra; Ngoc Pham; Sarah Prats; David M. Plouffe; Sally-Ann Poulsen; Anupam Pradhan; Celia Quevedo; Ronald J. Quinn; Christopher A. Rice; Mohamed Abdo Rizk; Andrea Ruecker; Robert St Onge; Rafaela Salgado Ferreira; Jasmeet Samra; Natalie G. Robinett; Ulrich Schlecht; Marjorie Schmitt; Filipe Silva Villela; Francesco Silvestrini; Robert Sinden; Dennis A. Smith; Thierry Soldati; Andreas Spitzmueller; Serge Maximilian Stamm; David J. Sullivan; William Sullivan; Sundari Suresh; Brian M. Suzuki; Yo Suzuki; S. Joshua Swamidass; Donatella Taramelli; Lauve R. Y. Tchokouaha; Anjo Theron; David Thomas; Kathryn F. Tonissen; Simon Townson; Abhai K. Tripathi; Valentin Trofimov; Kenneth O. Udenze; Imran Ullah; Cindy Vallieres; Edgar Vigil; Joseph M. Vinetz; Phat Voong Vinh; Hoan Vu; Nao-aki Watanabe; Kate Weatherby; Pamela M. White; Andrew F. Wilks; Elizabeth A. Winzeler; Edward Wojcik; Melanie Wree; Wesley Wu; Naoaki Yokoyama; Paul H. A. Zollo; Nada Abla; Benjamin Blasco; Jeremy Burrows; Benoit Laleu; Didier Leroy; Thomas Spangenberg; Timothy Wells; Paul A. Willis

doi:10.1371/journal.ppat.1005763

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

Journal article

Open access

Peer reviewed

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

Wesley C. Van Voorhis, John H. Adams, Roberto Adelfio, Vida Ahyong, Myles H. Akabas, Pietro Alano, Aintzane Alday, Yesmalie Aleman Resto, Aishah Alsibaee, Ainhoa Alzualde, …

PLoS pathogens, Vol.12(7), pp.e1005763-e1005763

28/07/2016

DOI: https://doi.org/10.1371/journal.ppat.1005763

PMCID: PMC4965013

PMID: 27467575

Abstract

Life Sciences & Biomedicine

Microbiology

Parasitology

Science & Technology

Virology

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.

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Title: Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
Creators - without role: Wesley C. Van Voorhis - University of Washington
John H. Adams - Univ S Florida, Dept Global Hlth, Ctr Global Hlth & Infect Dis Res, Tampa, FL USA
Roberto Adelfio - College Station Medical Center
Vida Ahyong - MED Institute
Myles H. Akabas - Albert Einstein College of Medicine
Pietro Alano - Ist Super Sanita, Dipartimento Malattie Infett Parassitarie & Immun, Rome, Italy
Aintzane Alday - BBD BioPhenix SL BIOBIDE, Donostia San Sebastian, Gipuzkoa, Spain
Yesmalie Aleman Resto - Bigelow Lab Ocean Sci, East Boothbay, ME USA
Aishah Alsibaee - Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland
Ainhoa Alzualde - BBD BioPhenix SL BIOBIDE, Donostia San Sebastian, Gipuzkoa, Spain
Katherine T. Andrews - Griffith University
Simon V. Avery - University of Nottingham
Vicky M. Avery - Griffith University
Lawrence Ayong - Institute of Technology of Cambodia
Mark Baker - Novartis
Stephen Baker - University of Oxford
Choukri Ben Mamoun - Yale University
Sangeeta Bhatia - College Station Medical Center
Quentin Bickle - Supreme Council Of Health
Lotfi Bounaadja - Sorbonne Université
Tana Bowling - Scynexis
Juergen Bosch - Supreme Council Of Health
Lauren E. Boucher - Supreme Council Of Health
Fabrice F. Boyom - Univ Yaounde, Dept Biochem, Yaounde, Cameroon
Jose Brea - Universidade de Santiago de Compostela
Marian Brennan - Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland
Audrey Burton - Scynexis
Conor R. Caffrey - Univ Calif San Francisco, Dept Pathol, Ctr Discovery & Innovat Parasit Dis, San Francisco, CA 94140 USA
Grazia Camarda - Ist Super Sanita, Dipartimento Malattie Infett Parassitarie & Immun, Rome, Italy
Manuela Carrasquilla - Pennsylvania State University
Dee Carter - University of Sydney
Maria Belen Cassera - Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA
Ken Chih-Chien Cheng - NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA
Worathad Chindaudomsate - Mahidol University
Anthony Chubb - Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland
Beatrice L. Colon - College Station Medical Center
Daisy D. Colon-Lopez - Supreme Council Of Health
Yolanda Corbett - University of Milan
Gregory J. Crowther - University of Washington
Noemi Cowan - College Station Medical Center
Sarah D'Alessandro - University of Milan
Na Le Dang - Washington Univ, Dept Pathol & Immunol, St Louis, MO USA
Michael Delves - Imperial Coll London, Dept Life Sci, London, England
Joseph L. DeRisi - MED Institute
Alan Y. Du - Supreme Council Of Health
Sandra Duffy - Griffith University
Shimaa Abd El-Salam El-Sayed - College Station Medical Center
Michael T. Ferdig - University of Notre Dame
Jose A. Fernandez Robledo - Bigelow Lab Ocean Sci, East Boothbay, ME USA
David A. Fidock - Columbia University
Isabelle Florent - Sorbonne Université
Patrick V. T. Fokou - Univ Yaounde, Dept Biochem, Yaounde, Cameroon
Ani Galstian - Broad Institute
Francisco Javier Gamo - GlaxoSmithKline R&D, Biochem & Parasitol Dept, Malaria DPU, DDW, Madrid, Spain
Suzanne Gokool - College Station Medical Center
Ben Gold - College Station Medical Center
Todd Golub - Broad Institute
Gregory M. Goldgof - College Station Medical Center
Rajarshi Guha - NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA
W. Armand Guiguemde - St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, 332 N Lauderdale St, Memphis, TN 38105 USA
Nil Gural - College Station Medical Center
R. Kiplin Guy - St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, 332 N Lauderdale St, Memphis, TN 38105 USA
Michael A. E. Hansen - Institute of Technology of Cambodia
Kirsten K. Hanson - Univ Texas San Antonio, Dept Biol, San Antonio, TX USA
Andrew Hemphill - University of Bern
Rob Hooft van Huijsduijnen - College Station Medical Center
Takaaki Horii - Eisai & Co Ltd, Hhc Data Creat Ctr, Global Hlth Res Sect, Tsukuba, Ibaraki, Japan
Paul Horrocks - Keele University
Tyler B. Hughes - Washington Univ, Dept Pathol & Immunol, St Louis, MO USA
Christopher Huston - University of Vermont
Ikuo Igarashi - College Station Medical Center
Katrin Ingram-Sieber - College Station Medical Center
Maurice A. Itoe - College Station Medical Center
Ajit Jadhav - NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA
Amornrat Naranuntarat Jensen - Mahidol University
Laran T. Jensen - Mahidol University
Rays H. Y. Jiang - Univ S Florida, Dept Global Hlth, Ctr Global Hlth & Infect Dis Res, Tampa, FL USA
Annette Kaiser - College Station Medical Center
Jennifer Keiser - College Station Medical Center
Thomas Ketas - College Station Medical Center
Sebastien Kicka - University of Geneva
Sunyoung Kim - LSU Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA USA
Kiaran Kirk - Supreme Council Of Health
Vidya P. Kumar - Yale University
Dennis E. Kyle - Univ S Florida, Dept Global Hlth, Ctr Global Hlth & Infect Dis Res, Tampa, FL USA
Maria Jose Lafuente - GlaxoSmithKline R&D, Biochem & Parasitol Dept, Malaria DPU, DDW, Madrid, Spain
Scott Landfear - Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA
Nathan Lee - College Station Medical Center
Sukjun Lee - Institute of Technology of Cambodia
Adele M. Lehane - Supreme Council Of Health
Fengwu Li - Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA
David Little - College Station Medical Center
Liqiong Liu - LSU Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA USA
Manuel Llinas - Pennsylvania State University
Maria I. Loza - Universidade de Santiago de Compostela
Aristea Lubar - College Station Medical Center
Leonardo Lucantoni - Griffith University
Isabelle Lucet - Monash University
Louis Maes - University of Antwerp
Dalu Mancama - CSIR, Biosci Unit, Pretoria, South Africa
Nuha R. Mansour - Supreme Council Of Health
Sandra March - College Station Medical Center
Sheena McGowan - Monash University
Iset Medina Vera - College Station Medical Center
Stephan Meister - Supreme Council Of Health
Luke Mercer - Scynexis
Jordi Mestres - College Station Medical Center
Alvine N. Mfopa - Univ Yaounde, Dept Biochem, Yaounde, Cameroon
Raj N. Misra - NCI, Div Canc Therapeut & Diag, Drug Synth & Chem Branch, NIH, Bethesda, MD 20892 USA
Seunghyun Moon - Institute of Technology of Cambodia
John P. Moore - College Station Medical Center
Francielly Morais Rodrigues da Costa - Univ Fed Minas Gerais, Grad Program Bioinformat, Belo Horizonte, MG, Brazil
Joachim Mueller - University of Bern
Arantza Muriana - BBD BioPhenix SL BIOBIDE, Donostia San Sebastian, Gipuzkoa, Spain
Stephen Nakazawa Hewitt - University of Washington
Bakela Nare - Scynexis
Carl Nathan - College Station Medical Center
Nathalie Narraidoo - University of Nottingham
Sujeevi Nawaratna - Griffith University
Kayode K. Ojo - University of Washington
Diana Ortiz - Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA
Gordana Panic - College Station Medical Center
George Papadatos - EBI, EMBL, ChEMBL Grp, Hinxton, Cambs, England
Silvia Parapini - University of Milan
Kailash Patra - College Station Medical Center
Ngoc Pham - Griffith University
Sarah Prats - GlaxoSmithKline R&D, Biochem & Parasitol Dept, Malaria DPU, DDW, Madrid, Spain
David M. Plouffe - Novartis Res Fdn, Genom Inst, San Diego, CA USA
Sally-Ann Poulsen - Griffith University
Anupam Pradhan - Univ S Florida, Dept Global Hlth, Ctr Global Hlth & Infect Dis Res, Tampa, FL USA
Celia Quevedo - BBD BioPhenix SL BIOBIDE, Donostia San Sebastian, Gipuzkoa, Spain
Ronald J. Quinn - Griffith University
Christopher A. Rice - Univ S Florida, Dept Global Hlth, Ctr Global Hlth & Infect Dis Res, Tampa, FL USA
Mohamed Abdo Rizk - College Station Medical Center
Andrea Ruecker - Imperial Coll London, Dept Life Sci, London, England
Robert St Onge - Stanford University
Rafaela Salgado Ferreira - Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
Jasmeet Samra - Pennsylvania State University
Natalie G. Robinett - Supreme Council Of Health
Ulrich Schlecht - Stanford University
Marjorie Schmitt - IRJBD, Lab Chim Mol, COB, CNRS,UMR 7509, Mulhouse, France
Filipe Silva Villela - Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
Francesco Silvestrini - Ist Super Sanita, Dipartimento Malattie Infett Parassitarie & Immun, Rome, Italy
Robert Sinden - University of Oxford
Dennis A. Smith - University of Cape Town
Thierry Soldati - University of Geneva
Andreas Spitzmueller - College Station Medical Center
Serge Maximilian Stamm - Supreme Council Of Health
David J. Sullivan - Supreme Council Of Health
William Sullivan - Univ Calif Santa Cruz, Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA
Sundari Suresh - Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
Brian M. Suzuki - Univ Calif San Francisco, Dept Pathol, Ctr Discovery & Innovat Parasit Dis, San Francisco, CA 94140 USA
Yo Suzuki - J. Craig Venter Institute
S. Joshua Swamidass - Imperial Coll London, Dept Life Sci, London, England
Donatella Taramelli - Washington Univ, Dept Pathol & Immunol, St Louis, MO USA
Lauve R. Y. Tchokouaha - Univ Yaounde, Dept Biochem, Yaounde, Cameroon
Anjo Theron - CSIR, Biosci Unit, Pretoria, South Africa
David Thomas - Broad Institute
Kathryn F. Tonissen - Griffith University
Simon Townson - College Station Medical Center
Abhai K. Tripathi - Supreme Council Of Health
Valentin Trofimov - University of Geneva
Kenneth O. Udenze - Univ S Florida, Dept Global Hlth, Ctr Global Hlth & Infect Dis Res, Tampa, FL USA
Imran Ullah - Keele University
Cindy Vallieres - University of Nottingham
Edgar Vigil - Supreme Council Of Health
Joseph M. Vinetz - College Station Medical Center
Phat Voong Vinh - University of Oxford
Hoan Vu - Griffith University
Nao-aki Watanabe - Eisai & Co Ltd, Hhc Data Creat Ctr, Global Hlth Res Sect, Tsukuba, Ibaraki, Japan
Kate Weatherby - University of Sydney
Pamela M. White - Univ Calif Santa Cruz, Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA
Andrew F. Wilks - Hudson Institute
Elizabeth A. Winzeler - Supreme Council Of Health
Edward Wojcik - LSU Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA USA
Melanie Wree - Supreme Council Of Health
Wesley Wu - MED Institute
Naoaki Yokoyama - College Station Medical Center
Paul H. A. Zollo - Univ Yaounde, Dept Biochem, Yaounde, Cameroon
Nada Abla - College Station Medical Center
Benjamin Blasco - College Station Medical Center
Jeremy Burrows - College Station Medical Center
Benoit Laleu - College Station Medical Center
Didier Leroy - College Station Medical Center
Thomas Spangenberg - College Station Medical Center
Timothy Wells - College Station Medical Center
Paul A. Willis - College Station Medical Center
Publication Details: PLoS pathogens, Vol.12(7), pp.e1005763-e1005763
Publisher: Public Library Science
Number of pages: 23
Grant note: Bloomberg Family Foundation (JBr) MMV 12/0048; MMV 12/0076 / Medicines for Malaria Venture MMV Challenge Grant V6YBT51 / South African Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); South Africa Medical Research Council (SAMRC) 16H02768 / Grants-in-Aid for Scientific Research; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research (KAKENHI) Bill and Melinda Gates Foundation Grand Challenges Explorations; Bill & Melinda Gates Foundation ANR-12-BS07-0020-01 / French ANR program Mammamia; Agence Nationale de la Recherche (ANR) UK DFID FT10100185; FT0991213; LP120200557 / Australian Research Council DGE-1232825 / National Science Foundation Graduate Research Fellowship Program; National Science Foundation (NSF) JHMRI V1YTB95 / Council for Scientific and Industrial Research; Council of Scientific & Industrial Research (CSIR) - India OPP1040394; OPP1040399; OPP1086189; OPP1069393; OPP1119049; OPP1024029 / Bill & Melinda Gates Foundation; CGIAR T32GM080189; R01GM104486; R01AI117017 / US NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Identifiers: 9948226108331
Academic Unit: King Saud University
Language: English
Resource Type: Journal article