Wesley C. Van VoorhisJohn H. AdamsRoberto AdelfioVida AhyongMyles H. AkabasPietro AlanoAintzane AldayYesmalie Alemán RestoAishah AlsibaeeAinhoa AlzualdeKatherine T. AndrewsSimon V. AveryVicky M. AveryLawrence AyongMark BakerStephen BakerChoukri Ben MamounSangeeta BhatiaQuentin BickleLotfi BounaadjaTana BowlingJürgen BoschLauren E. BoucherFabrice F. BoyomJose BreaMarian BrennanAudrey BurtonConor R. CaffreyGrazia CamardaManuela CarrasquillaDee CarterMaria Belen CasseraKen Chih-Chien ChengWorathad ChindaudomsateAnthony ChubbBeatrice L. ColonDaisy D. Colón-LópezYolanda CorbettGregory J. CrowtherNoemi CowanSarah D’AlessandroNa Le DangMichael DelvesJoseph L. DeRisiAlan Y. DuSandra DuffyShimaa Abd El-Salam El-SayedMichael T. FerdigJosé A. Fernández RobledoDavid A. FidockIsabelle FlorentPatrick V.T. FokouAni GalstianFrancisco Javier GamoSuzanne GokoolBen GoldTodd GolubGregory M. GoldgofRajarshi GuhaW. Armand GuiguemdeNil GuralR. Kiplin GuyMichael A.E. HansenKirsten K. HansonAndrew HemphillRob Hooft van HuijsduijnenTakaaki HoriiPaul HorrocksTyler B. HughesChristopher HustonIkuo IgarashiKatrin Ingram-SieberMaurice A. ItoeAjit JadhavAmornrat Naranuntarat JensenLaran T. JensenRays H.Y. JiangAnnette KaiserJennifer KeiserThomas KetasSebastien KickaSunyoung KimKiaran KirkVidya P. KumarDennis E. KyleMaria Jose LafuenteScott LandfearNathan LeeSukjun LeeAdele M. LehaneUniversity of Washington, SeattleUniversity of South Florida, TampaSwiss Tropical and Public Health Institute (Swiss TPH)Universitat BaselUniversity of California, San FranciscoAlbert Einstein College of Medicine of Yeshiva UniversityIstituto Superiore Di SanitaBiobideBigelow Laboratory for Ocean SciencesRoyal College of Surgeons in IrelandGriffith UniversityQIMR Berghofer Medical Research InstituteUniversity of NottinghamInstitut Pasteur KoreaClinical Pharmacology and NephrologyUCLNuffield Department of Clinical MedicineLondon School of Hygiene & Tropical MedicineYale UniversityMassachusetts Institute of TechnologyMuseum National d'Histoire NaturelleScynexis, Inc.Johns Hopkins Bloomberg School of Public HealthUniversite de Yaounde IUniversidad de Santiago de CompostelaPennsylvania State UniversityThe University of SydneyVirginia Polytechnic Institute and State UniversityNational Center for Advancing Translational SciencesMahidol UniversityUniversity of South Florida, Morsani College of MedicineUniversità degli Studi di MilanoWashington University in St. LouisImperial College LondonUniversity of California, San DiegoObihiro University of Agriculture and Veterinary MedicineMansoura UniversityUniversity of Notre DameColumbia University Medical CenterBroad InstituteGlaxoSmithKline plc, SpainNorthwick Park HospitalWeill Cornell Medical CollegeSt. Jude Children's Research HospitalUniversity of Texas at San AntonioUniversity of Lisbon Faculty of Medicine, Institute of Molecular MedicineUniversity of BernMedicines for Malaria VentureEisai Co., Ltd.Keele UniversityUniversity of Vermont College of MedicineInstitute of PharmacogeneticsUniversité de GenèveLSU Health Sciences Center - New OrleansResearch School of Biologyn National UniversityOregon Health and Science UniversityMonash UniversityUniversiteit AntwerpenThe Council for Scientific and Industrial ResearchWellcome Trust Sanger Institute2018-12-112019-03-142018-12-112019-03-142016-07-01PLoS Pathogens. Vol.12, No.7 (2016)15537374155373662-s2.0-84982980463https://repository.li.mahidol.ac.th/handle/20.500.14594/43004© 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyArticleSCOPUS10.1371/journal.ppat.1005763