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.

journal_name

Nature

journal_title

Nature

authors

Baragaña B,Hallyburton I,Lee MC,Norcross NR,Grimaldi R,Otto TD,Proto WR,Blagborough AM,Meister S,Wirjanata G,Ruecker A,Upton LM,Abraham TS,Almeida MJ,Pradhan A,Porzelle A,Luksch T,Martínez MS,Luksch T,Bolscher JM,

doi

10.1038/nature14451

subject

Has Abstract

pub_date

2015-06-18 00:00:00

pages

315-20

issue

7556

eissn

0028-0836

issn

1476-4687

pii

nature14451

journal_volume

522

pub_type

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