RT Journal Article
T1 Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
A1 Van Voorhis, Wesley C.
A1 Adams, John H.
A1 Adelfio, Roberto
A1 Ahyong, Vida
A1 Akabas, Myles H.
A1 Alano, Pietro
A1 Alday, Aintzane
A1 Alemán Resto, Yesmalie
A1 Alsibaee, Aishah
A1 Alzualde, Ainhoa
A1 Andrews, Katherine T.
A1 Avery, Simon V.
A1 Avery, Vicky M.
A1 Ayong, Lawrence
A1 Baker, Mark
A1 Baker, Stephen
A1 Ben Mamoun, Choukri
A1 Bhatia, Sangeeta
A1 Bickle, Quentin
A1 Bounaadja, Lotfi
A1 Bowling, Tana
A1 Bosch, Jürgen
A1 Boucher, Lauren E.
A1 Boyom, Fabrice F.
A1 Brennan, Marian
A1 Burton, Audrey
A1 Caffrey, Conor R.
A1 Camarda, Grazia
A1 Carrasquilla, Manuela
A1 Carter, Dee
A1 Belen Cassera, Maria
A1 Chih-Chien Cheng, Ken
A1 Chindaudomsate, Worathad
A1 Chubb, Anthony
A1 Colon, Beatrice L.
A1 Colón-López, Daisy D.
A1 Corbett, Yolanda
A1 Crowther, Gregory J.
A1 Cowan, Noemi
A1 D’Alessandro, Sarah
A1 Le Dang, Na
A1 Delves, Michael
A1 DeRisi, Joseph L.
A1 Du, Alan Y.
A1 Duffy, Sandra
A1 Abd El-Salam El-Sayed, Shimaa
A1 Ferdig, Michael T.
A1 Fernández Robledo, José A.
A1 Fidock, David A.
A1 Florent, Isabelle
A1 Fokou, Patrick V. T.
A1 Galstian, Ani
A1 Gamo, Francisco Javier
A1 Gokool, Suzanne
A1 Gold, Ben
A1 Golub, Todd
A1 Goldgof, Gregory M.
A1 Guha, Rajarshi
A1 Guiguemde, W. Armand
A1 Gural, Nil
A1 Guy, R. Kiplin
A1 Hansen, Michael A. E.
A1 Hanson, Kirsten K.
A1 Hemphill, Andrew
A1 Hooft van Huijsduijnen, Rob
A1 Horii, Takaaki
A1 Horrocks, Paul
A1 Hughes, Tyler B.
A1 Huston, Christopher
A1 Igarashi, Ikuo
A1 Ingram-Sieber, Katrin
A1 Itoe, Maurice A.
A1 Jadhav, Ajit
A1 Naranuntarat Jensen, Amornrat
A1 Jensen, Laran T.
A1 Jiang, Rays H. Y.
A1 Kaiser, Annette
A1 Keiser, Jennifer
A1 Ketas, Thomas
A1 Kicka, Sebastien
A1 Kim, Sunyoung
A1 Kirk, Kiaran
A1 Kumar, Vidya P.
A1 Kyle, Dennis E.
A1 Lafuente, Maria Jose
A1 Landfear, Scott
A1 Lee, Nathan
A1 Lee, Sukjun
A1 Lehane, Adele M.
A1 Li, Fengwu
A1 Little, David
A1 Liu, Liqiong
A1 Llinás, Manuel
A1 Lubar, Aristea
A1 Lucantoni, Leonardo
A1 Lucet, Isabelle
A1 Maes, Louis
A1 Mancama, Dalu
A1 Mansour, Nuha R.
A1 March, Sandra
A1 McGowan, Sheena
A1 Medina Vera, Iset
A1 Meister, Stephan
A1 Mercer, Luke
A1 Mestres, Jordi
A1 Mfopa, Alvine N.
A1 Misra, Raj N.
A1 Moon, Seunghyun
A1 Moore, John P.
A1 Morais Rodrigues da Costa, Francielly
A1 Müller, Joachim
A1 Muriana, Arantza
A1 Nakazawa Hewitt, Stephen
A1 Nare, Bakela
A1 Nathan, Carl
A1 Narraidoo, Nathalie
A1 Nawaratna, Sujeevi
A1 Ojo, Kayode K.
A1 Ortiz, Diana
A1 Panic, Gordana
A1 Papadatos, George
A1 Parapini, Silvia
A1 Patra, Kailash
A1 Pham, Ngoc
A1 Prats, Sarah
A1 Plouffe, David M.
A1 Poulsen, Sally-Ann
A1 Pradhan, Anupam
A1 Quevedo, Celia
A1 Quinn, Ronald J.
A1 Rice, Christopher A.
A1 Abdo Rizk, Mohamed
A1 Ruecker, Andrea
A1 St. Onge, Robert
A1 Salgado Ferreira, Rafaela
A1 Samra, Jasmeet
A1 Robinett, Natalie G.
A1 Schlecht, Ulrich
A1 Schmitt, Marjorie
A1 Silva Villela, Filipe
A1 Silvestrini, Francesco
A1 Sinden, Robert
A1 Smith, Dennis A.
A1 Soldati, Thierry
A1 Spitzmüller, Andreas
A1 Stamm, Serge Maximilian
A1 Sullivan, David J.
A1 Sullivan, William
A1 Suresh, Sundari
A1 Suzuki, Brian M.
A1 Suzuki, Yo
A1 Swamidass, S. Joshua
A1 Taramelli, Donatella
A1 Tchokouaha, Lauve R. Y.
A1 Theron, Anjo
A1 Thomas, David
A1 Tonissen, Kathryn F.
A1 Townson, Simon
A1 Tripathi, Abhai K.
A1 Trofimov, Valentin
A1 Udenze, Kenneth O.
A1 Ullah, Imran
A1 Vallieres, Cindy
A1 Vigil, Edgar
A1 Vinetz, Joseph M.
A1 Voong Vinh, Phat
A1 Vu, Hoan
A1 Watanabe, Nao-aki
A1 Weatherby, Kate
A1 White, Pamela M.
A1 Wilks, Andrew F.
A1 Winzeler, Elizabeth A.
A1 Wojcik, Edward
A1 Wree, Melanie
A1 Wu, Wesley
A1 Yokoyama, Naoaki
A1 Zollo, Paul H. A.
A1 Abla, Nada
A1 Blasco, Benjamin
A1 Burrows, Jeremy
A1 Laleu, Benoît
A1 Leroy, Didier
A1 Spangenberg, Thomas
A1 Wells, Timothy
A1 Willis, Paul A.
A1 Brea Floriani, José Manuel
A1 Loza García, María Isabel
AB 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.
PB PLOS Pathogens
SN 1553-7366
YR 2016
FD 2016-07-28
LK https://hdl.handle.net/10347/44729
UL https://hdl.handle.net/10347/44729
LA eng
NO Van Voorhis WC, Adams JH, Adelfio R, Ahyong V, Akabas MH, Alano P, et al. (2016) Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond. PLoS Pathog 12(7): e1005763. doi:10.1371/journal.ppat.1005763
DS Minerva
RD 23 abr 2026