ddd107498 has been researched along with Malaria* in 3 studies
3 other study(ies) available for ddd107498 and Malaria
| Article | Year |
|---|---|
Discovery of a Quinoline-4-carboxamide Derivative with a Novel Mechanism of Action, Multistage Antimalarial Activity, and Potent in Vivo Efficacy.
Topics: Animals; Antimalarials; Disease Models, Animal; Drug Discovery; Malaria; Mice; Molecular Structure; Plasmodium falciparum; Quinolines; Structure-Activity Relationship | 2016 |
In Vivo and In Vitro Optimization of Screening Antimalarial Hits toward Lead Molecules for Preclinical Development.
In order to overcome one of the greatest challenges in malaria treatment, drug resistance, new drug candidates are urgently needed, which should preferably act via novel mechanisms. Successful optimization of a phenotypic screening hit based on a quinoline-4-carboxamide derivative resulted in the highly promising lead structure 4, which according to the Medicines for Malaria Venture (MMV) met the efficacy and drug metabolism and pharmacokinetics (DMPK) requirements for a malaria drug target candidate and consequently was selected for preclinical development. Topics: Antimalarials; Drug Evaluation, Preclinical; Humans; Malaria; Molecular Structure; Plasmodium falciparum; Quinolines; Structure-Activity Relationship | 2016 |
A novel multiple-stage antimalarial agent that inhibits protein synthesis.
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. Topics: Animals; Antimalarials; Drug Discovery; Female; Gene Expression Regulation; Life Cycle Stages; Liver; Malaria; Male; Models, Molecular; Peptide Elongation Factor 2; Plasmodium; Plasmodium berghei; Plasmodium falciparum; Plasmodium vivax; Protein Biosynthesis; Quinolines | 2015 |