Van Voorhis, Wesley CWesley CVan VoorhisAdams, John HJohn HAdamsAdelfio, RobertoRobertoAdelfioAhyong, VidaVidaAhyongAkabas, Myles HMyles HAkabasAlano, PietroPietroAlanoAlday, AintzaneAintzaneAldayAlemán Resto, YesmalieYesmalieAlemán RestoAlsibaee, AishahAishahAlsibaeeAlzualde, AinhoaAinhoaAlzualdeAndrews, Katherine TKatherine TAndrewsAvery, Simon VSimon VAveryAvery, Vicky MVicky MAveryAyong, LawrenceLawrenceAyongBaker, MarkMarkBakerBaker, StephenStephenBakerBen Mamoun, ChoukriChoukriBen MamounBhatia, SangeetaSangeetaBhatiaBickle, QuentinQuentinBickleBounaadja, LotfiLotfiBounaadjaBowling, TanaTanaBowlingBosch, JürgenJürgenBoschBoucher, Lauren ELauren EBoucherBoyom, Fabrice FFabrice FBoyomBrea, JoseJoseBreaBrennan, MarianMarianBrennanBurton, AudreyAudreyBurtonCaffrey, Conor RConor RCaffreyCamarda, GraziaGraziaCamardaCarrasquilla, ManuelaManuelaCarrasquillaCarter, DeeDeeCarterBelen Cassera, MariaMariaBelen CasseraChih-Chien Cheng, KenKenChih-Chien ChengChindaudomsate, WorathadWorathadChindaudomsateChubb, AnthonyAnthonyChubbColon, Beatrice LBeatrice LColonColón-López, Daisy DDaisy DColón-LópezCorbett, YolandaYolandaCorbettCrowther, Gregory JGregory JCrowtherCowan, NoemiNoemiCowanD'Alessandro, SarahSarahD'AlessandroLe Dang, NaNaLe DangDelves, MichaelMichaelDelvesDeRisi, Joseph LJoseph LDeRisiDu, Alan YAlan YDuDuffy, SandraSandraDuffyAbd El-Salam El-Sayed, ShimaaShimaaAbd El-Salam El-SayedFerdig, Michael TMichael TFerdigFernández Robledo, José AJosé AFernández RobledoFidock, David ADavid AFidockFlorent, IsabelleIsabelleFlorentFokou, Patrick V TPatrick V TFokouGalstian, AniAniGalstianGamo, Francisco JavierFrancisco JavierGamoGokool, SuzanneSuzanneGokoolGold, BenBenGoldGolub, ToddToddGolubGoldgof, Gregory MGregory MGoldgofGuha, RajarshiRajarshiGuhaGuiguemde, W ArmandW ArmandGuiguemdeGural, NilNilGuralGuy, R KiplinR KiplinGuyHansen, Michael A EMichael A EHansenHanson, Kirsten KKirsten KHansonHemphill, AndrewAndrewHemphillHooft van Huijsduijnen, RobRobHooft van HuijsduijnenHorii, TakaakiTakaakiHoriiHorrocks, PaulPaulHorrocksHughes, Tyler BTyler BHughesHuston, ChristopherChristopherHustonIgarashi, IkuoIkuoIgarashiIngram-Sieber, KatrinKatrinIngram-SieberItoe, Maurice AMaurice AItoeJadhav, AjitAjitJadhavNaranuntarat Jensen, AmornratAmornratNaranuntarat JensenJensen, Laran TLaran TJensenJiang, Rays H YRays H YJiangKaiser, AnnetteAnnetteKaiserKeiser, JenniferJenniferKeiserKetas, ThomasThomasKetasKicka, SebastienSebastienKickaKim, SunyoungSunyoungKimKirk, KiaranKiaranKirkKumar, Vidya PVidya PKumarKyle, Dennis EDennis EKyleLafuente, Maria JoseMaria JoseLafuenteLandfear, ScottScottLandfearLee, NathanNathanLeeLee, SukjunSukjunLeeLehane, Adele MAdele MLehaneLi, FengwuFengwuLiLittle, DavidDavidLittleLiu, LiqiongLiqiongLiuLlinás, ManuelManuelLlinásLoza, Maria IMaria ILozaLubar, AristeaAristeaLubarLucantoni, LeonardoLeonardoLucantoniLucet, IsabelleIsabelleLucetMaes, LouisLouisMaesMancama, DaluDaluMancamaMansour, Nuha RNuha RMansourMarch, SandraSandraMarchMcGowan, SheenaSheenaMcGowanMedina Vera, IsetIsetMedina VeraMeister, StephanStephanMeisterMercer, LukeLukeMercerMestres, JordiJordiMestresMfopa, Alvine NAlvine NMfopaMisra, Raj NRaj NMisraMoon, SeunghyunSeunghyunMoonMoore, John PJohn PMooreMorais Rodrigues da Costa, FranciellyFranciellyMorais Rodrigues da CostaMüller, Heinz JoachimHeinz JoachimMüllerMuriana, ArantzaArantzaMurianaNakazawa Hewitt, StephenStephenNakazawa HewittNare, BakelaBakelaNareNathan, CarlCarlNathanNarraidoo, NathalieNathalieNarraidooNawaratna, SujeeviSujeeviNawaratnaOjo, Kayode KKayode KOjoOrtiz, DianaDianaOrtizPanic, GordanaGordanaPanicPapadatos, GeorgeGeorgePapadatosParapini, SilviaSilviaParapiniPatra, KailashKailashPatraPham, NgocNgocPhamPrats, SarahSarahPratsPlouffe, David MDavid MPlouffePoulsen, Sally-AnnSally-AnnPoulsenPradhan, AnupamAnupamPradhanQuevedo, CeliaCeliaQuevedoQuinn, Ronald JRonald JQuinnRice, Christopher AChristopher ARiceAbdo Rizk, MohamedMohamedAbdo RizkRuecker, AndreaAndreaRueckerSt Onge, RobertRobertSt OngeSalgado Ferreira, RafaelaRafaelaSalgado FerreiraSamra, JasmeetJasmeetSamraRobinett, Natalie GNatalie GRobinettSchlecht, UlrichUlrichSchlechtSchmitt, MarjorieMarjorieSchmittSilva Villela, FilipeFilipeSilva VillelaSilvestrini, FrancescoFrancescoSilvestriniSinden, RobertRobertSindenSmith, Dennis ADennis ASmithSoldati, ThierryThierrySoldatiSpitzmüller, AndreasAndreasSpitzmüllerStamm, Serge MaximilianSerge MaximilianStammSullivan, David JDavid JSullivanSullivan, WilliamWilliamSullivanSuresh, SundariSundariSureshSuzuki, Brian MBrian MSuzukiSuzuki, YoYoSuzukiSwamidass, S JoshuaS JoshuaSwamidassTaramelli, DonatellaDonatellaTaramelliTchokouaha, Lauve R YLauve R YTchokouahaTheron, AnjoAnjoTheronThomas, DavidDavidThomasTonissen, Kathryn FKathryn FTonissenTownson, SimonSimonTownsonTripathi, Abhai KAbhai KTripathiTrofimov, ValentinValentinTrofimovUdenze, Kenneth OKenneth OUdenzeUllah, ImranImranUllahVallieres, CindyCindyVallieresVigil, EdgarEdgarVigilVinetz, Joseph MJoseph MVinetzVoong Vinh, PhatPhatVoong VinhVu, HoanHoanVuWatanabe, Nao-AkiNao-AkiWatanabeWeatherby, KateKateWeatherbyWhite, Pamela MPamela MWhiteWilks, Andrew FAndrew FWilksWinzeler, Elizabeth AElizabeth AWinzelerWojcik, EdwardEdwardWojcikWree, MelanieMelanieWreeWu, WesleyWesleyWuYokoyama, NaoakiNaoakiYokoyamaZollo, Paul H APaul H AZolloAbla, NadaNadaAblaBlasco, BenjaminBenjaminBlascoBurrows, JeremyJeremyBurrowsLaleu, BenoîtBenoîtLaleuLeroy, DidierDidierLeroySpangenberg, ThomasThomasSpangenbergWells, TimothyTimothyWellsWillis, Paul APaul AWillis2025-01-082025-01-082016-07https://boris-portal.unibe.ch/handle/20.500.12422/198972A 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.en600 - Technology::630 - Agriculture500 - Science::570 - Life sciences; biology500 - Science::590 - Animals (Zoology)article10.7892/boris.966352746757510.1371/journal.ppat.1005763