Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 315-320 |
| Number of pages | 6 |
| Journal | Nature |
| Volume | 522 |
| Issue number | 7556 |
| DOIs | |
| Publication status | Published - 18 Jun 2015 |
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A novel multiple-stage antimalarial agent that inhibits protein synthesis. / Baragana, Beatriz; Hallyburton, Irene; Lee, Marcus C. S.; Norcross, Neil R.; Grimaldi, Raffaella; Otto, Thomas D.; Proto, William R.; Blagborough, Andrew M.; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M.; Abraham, Tara S.; Almeida, Mariana J.; Pradhan, Anupam; Porzelle, Achim; Santos Martinez, Maria; Bolscher, Judith M.; Woodland, Andrew; Luksch, Torsten; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M.; Churcher, Tom S.; Sala, Katarzyna A.; Zakutansky, Sara E.; Belén Jiménez-Díaz, María ; Maria Sanz, Laura; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M.; Sauerwein, Robert W.; Dechering, Koen J.; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A.; Angulo-Barturen, Inigo; Ferrer-Bazaga, Santiago; Javier Gamo, Francisco; Wyatt, Paul G.; Leroy, Didier; Siegl, Peter; Delves, Michael J.; Kyle, Dennis E.; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N.; Sinden, Robert E.; Winzeler, Elizabeth A.; Charman, Susan A.; Bebrevska, Lidiya; Gray, David W.; Campbell, Simon; Fairlamb, Alan H.; Willis, Paul A.; Rayner, Julian C.; Fidock, David A.; Read, Kevin D. (Lead / Corresponding author); Gilbert, Ian H. (Lead / Corresponding author).
In: Nature, Vol. 522, No. 7556, 18.06.2015, p. 315-320.Research output: Contribution to journal › Article
TY - JOUR
T1 - A novel multiple-stage antimalarial agent that inhibits protein synthesis
AU - Baragana, Beatriz
AU - Hallyburton, Irene
AU - Lee, Marcus C. S.
AU - Norcross, Neil R.
AU - Grimaldi, Raffaella
AU - Otto, Thomas D.
AU - Proto, William R.
AU - Blagborough, Andrew M.
AU - Meister, Stephan
AU - Wirjanata, Grennady
AU - Ruecker, Andrea
AU - Upton, Leanna M.
AU - Abraham, Tara S.
AU - Almeida, Mariana J.
AU - Pradhan, Anupam
AU - Porzelle, Achim
AU - Santos Martinez, Maria
AU - Bolscher, Judith M.
AU - Woodland, Andrew
AU - Luksch, Torsten
AU - Norval, Suzanne
AU - Zuccotto, Fabio
AU - Thomas, John
AU - Simeons, Frederick
AU - Stojanovski, Laste
AU - Osuna-Cabello, Maria
AU - Brock, Paddy M.
AU - Churcher, Tom S.
AU - Sala, Katarzyna A.
AU - Zakutansky, Sara E.
AU - Belén Jiménez-Díaz, María
AU - Maria Sanz, Laura
AU - Riley, Jennifer
AU - Basak, Rajshekhar
AU - Campbell, Michael
AU - Avery, Vicky M.
AU - Sauerwein, Robert W.
AU - Dechering, Koen J.
AU - Noviyanti, Rintis
AU - Campo, Brice
AU - Frearson, Julie A.
AU - Angulo-Barturen, Inigo
AU - Ferrer-Bazaga, Santiago
AU - Javier Gamo, Francisco
AU - Wyatt, Paul G.
AU - Leroy, Didier
AU - Siegl, Peter
AU - Delves, Michael J.
AU - Kyle, Dennis E.
AU - Wittlin, Sergio
AU - Marfurt, Jutta
AU - Price, Ric N.
AU - Sinden, Robert E.
AU - Winzeler, Elizabeth A.
AU - Charman, Susan A.
AU - Bebrevska, Lidiya
AU - Gray, David W.
AU - Campbell, Simon
AU - Fairlamb, Alan H.
AU - Willis, Paul A.
AU - Rayner, Julian C.
AU - Fidock, David A.
AU - Read, Kevin D.
AU - Gilbert, Ian H.
PY - 2015/6/18
Y1 - 2015/6/18
N2 - 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.
AB - 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.
U2 - 10.1038/nature14451
DO - 10.1038/nature14451
M3 - Article
C2 - 26085270
VL - 522
SP - 315
EP - 320
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7556
ER -