A novel multiple-stage antimalarial agent that inhibits protein synthesis
File(s)
Author(s)
Type
Journal Article
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.
Date Issued
2015-06-18
Date Acceptance
2015-04-07
Citation
Nature, 2015, 522 (7556), pp.315-320
ISSN
0028-0836
Publisher
NATURE PUBLISHING GROUP
Start Page
315
End Page
320
Journal / Book Title
Nature
Volume
522
Issue
7556
Copyright Statement
Copyright © 2015, Rights Managed by Nature Publishing Group
Sponsor
Medicines for Malaria Venture
Medical Research Council (MRC)
Medicines for Malaria Venture
Medicines for Malaria Venture
Medical Research Council (MRC)
Grant Number
MMV 12/2800
MR/K010174/1B
MMV 08/2800
MMV 08/2800
MR/N00227X/1
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
ELONGATION-FACTOR 2
PLASMODIUM-FALCIPARUM
NEXT-GENERATION
MALARIA CONTROL
DRUG DISCOVERY
TRANSMISSION
POPULATIONS
VIVAX
IDENTIFICATION
GAMETOCYTES
Publication Status
Published