@article{9f29392ed28c4a62b18db04154a58d5c,
title = "A novel multiple-stage antimalarial agent that inhibits protein synthesis",
abstract = "There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.",
keywords = "antimalarial agent, artesunate, cycloheximide, dactinomycin, ddd 107498, elongation factor 2, guanosine triphosphate, messenger RNA, unclassified drug, DDD107498, quinoline derivative, disease control, disease transmission, parasite, protein, protozoan, animal cell, animal experiment, animal model, antimalarial activity, Article, controlled study, dose response, drug bioavailability, drug efficacy, drug safety, drug solubility, female, gene expression, human, human cell, life cycle stage, male, mouse, nonhuman, plasma half life, Plasmodium berghei, Plasmodium falciparum, priority journal, protein synthesis, ribosome, single drug dose, animal, antagonists and inhibitors, chemical structure, chemistry, drug development, drug effects, gene expression regulation, genetics, growth, development and aging, liver, malaria, metabolism, parasitology, physiology, Plasmodium, Plasmodium vivax, Plasmodium parasites, Animals, Antimalarials, Drug Discovery, Female, Gene Expression Regulation, Life Cycle Stages, Liver, Malaria, Male, Models, Molecular, Peptide Elongation Factor 2, Protein Biosynthesis, Quinolines",
author = "Beatriz Baraga{\~n}a and Irene Hallyburton and Lee, {Marcus C S} and Norcross, {Neil R.} and Raffaella Grimaldi and Otto, {Thomas D.} and Proto, {William R.} and Blagborough, {Andrew M.} and Stephan Meister and Grennady Wirjanata and Andrea Ruecker and Upton, {Leanna M.} and Abraham, {Tara S.} and Almeida, {Mariana J.} and Anupam Pradhan and Achim Porzelle and Mart{\'i}nez, {Mar{\'i}a Santos} and Bolscher, {Judith M.} and Andrew Woodland and Suzanne Norval and Fabio Zuccotto and John Thomas and Frederick Simeons and Laste Stojanovski and Maria Osuna-Cabello and Brock, {Paddy M.} and Churcher, {Tom S.} and Sala, {Katarzyna A.} and Zakutansky, {Sara E.} and Jim{\'e}nez-D{\'i}az, {Mar{\'i}a Bel{\'e}n} and Sanz, {Laura Maria} and Jennifer Riley and Rajshekhar Basak and Michael Campbell and Avery, {Vicky M.} and Sauerwein, {Robert W.} and Dechering, {Koen J.} and Rintis Noviyanti and Brice Campo and Frearson, {Julie A.} and I{\~n}igo Angulo-Barturen and Santiago Ferrer-Bazaga and Gamo, {Francisco Javier} and Wyatt, {Paul G.} and Didier Leroy and Peter Siegl and Delves, {Michael J.} and Kyle, {Dennis E.} and Sergio Wittlin and Jutta Marfurt and Price, {Ric N.} and Sinden, {Robert E.} and Winzeler, {Elizabeth A.} and Charman, {Susan A.} and Lidiya Bebrevska and Gray, {David W.} and Simon Campbell and Fairlamb, {Alan H.} and Willis, {Paul A.} and Rayner, {Julian C.} and Fidock, {David A.} and Read, {Kevin D.} and Gilbert, {Ian H.}",
year = "2015",
doi = "10.1038/nature14451",
language = "English",
volume = "22",
pages = "315--320",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7556",
}
