Details

Autor(en) / Beteiligte

• Baragaña, 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
• Martínez, María Santos
• 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.
• Jiménez-Díaz, María Belén
• Sanz, Laura Maria
• Riley, Jennifer
• Basak, Rajshekhar
• Campbell, Michael
• Avery, Vicky M.
• Sauerwein, Robert W.
• Dechering, Koen J.
• Noviyanti, Rintis
• Campo, Brice
• Frearson, Julie A.
• Angulo-Barturen, Iñigo
• Ferrer-Bazaga, Santiago
• Gamo, Francisco Javier
• 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.
• Gilbert, Ian H.

Titel

A novel multiple-stage antimalarial agent that inhibits protein synthesis

Ist Teil von

• Nature (London), 2015-06, Vol.522 (7556), p.315-320

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2015

Quelle

Psychology and Behavioral Sciences Collection (MeL)

Beschreibungen/Notizen

• 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. The description of a compound (DDD107498) with antimalarial activity against multiple life-cycle stages of Plasmodium falciparum and good pharmacokinetic and safety properties, with potential for single-dose treatment, chemoprotection and prevention of transmission. A new antimalarial agent With artemisinin resistance spreading, there is an urgent need to develop new therapeutics to target Plasmodium falciparum , the causative agent of malaria. Here Ian Gilbert and colleagues report the discovery of a compound (DDD107498) with antimalarial activity against multiple life-cycle stages of the parasite and good pharmacokinetic and safety properties. It is non-mutagenic and has potential for both single-dose treatment and once-weekly chemoprotection. DDD107498 acts through inhibition of cytosolic protein synthesis, with translation elongation factor eEF2 as its target.