A5103201290- Malaria Research and Control
- Computational Drug Discovery Methods
- Tuberculosis Research and Epidemiology
- Mosquito-borne diseases and control
- Insect Resistance and Genetics
- Invertebrate Immune Response Mechanisms
- Research on Leishmaniasis Studies
University of Glasgow
2018-2020
Targeting parasite's protein kinase Malaria elimination goals are constantly eroded by the challenge of emerging drug and insecticide resistance. Alam et al. have taken established targets—CLK kinases involved in regulation RNA splicing—and investigated how inhibition enzymes blocks completion its complex life cycle. They identified an inhibitor CLK that was 100-fold less active against most closely related human effective at clearing rodent malaria parasites. Not only does this compound...
The protein kinase PfCLK3 plays a critical role in the regulation of malarial parasite RNA splicing and is essential for survival blood stage Plasmodium falciparum. We recently validated as drug target malaria that offers prophylactic, transmission blocking, curative potential. Herein, we describe synthesis our initial hit TCMDC-135051 (1) efforts to establish structure–activity relationship with 7-azaindole-based series. A total 14 analogues were assessed time-resolved fluorescence energy...
Abstract The requirement for next generation anti-malarials to be both curative and transmission blockers necessitate the identification of molecular pathways essential viability asexual sexual parasite life stages. Here we identify a selective inhibitor Plasmodium falciparum protein kinase Pf CLK3 which use in combination with chemogenetics, whole genome sequencing transcriptomics validate as druggable target acting at multiple Consistent proposed role regulator RNA splicing, inhibition...
The kinase Pf CLK3 plays a critical role in the regulation of malarial parasite RNA splicing and is essential for survival blood stage Plasmodium falciparum . We recently validated as drug target malaria that offers prophylactic, transmission blocking curative potential. Herein we describe synthesis our initial hit TCMDC-135051 1 efforts to establish SAR with 7-azaindole-based series. A total 14 analogues were assessed TR-FRET assay against full recombinant protein 10 further parasites 3D7...
<p>The kinase <i>Pf</i>CLK3 plays a critical role in the regulation of malarial parasite RNA splicing and is essential for survival blood stage <i>Plasmodium falciparum</i>. We recently validated as drug target malaria that offers prophylactic, transmission blocking curative potential. Herein we describe synthesis our initial hit TCMDC-135051 <b>1</b>and efforts to establish SAR with 7-azaindole-based series. A total 14 analogues were assessed...