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Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing beta-galactosidase
- F. Buckner, C. Verlinde, A. L. La Flamme, W. V. Van Voorhis
- BiologyAntimicrobial agents and chemotherapy
- 1 November 1996
An assay with beta-galactosidase-expressing T. cruzi greatly simplifies screening drugs for selective anti-T.
Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors
It is shown that TgCDPK1 is inhibited by low nanomolar levels of bumped kinase inhibitors (BKIs), compounds inactive against mammalian kinases, and T. gondii expressing a glycine to methionine gatekeeper mutant enzyme show significantly decreased sensitivity to BKIs.
Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness
A selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection, underscores the possibility of developing a single class of drugs for these neglected diseases.
Heterologous expression of proteins from Plasmodium falciparum: results from 1000 genes.
Genomic-scale prioritization of drug targets: the TDR Targets database
The development of the TDR Targets database is discussed, which encompasses extensive genetic, biochemical and pharmacological data related to tropical disease pathogens, as well as computationally predicted druggability for potential targets and compound desirability information, and aims to facilitate the identification and prioritization of candidate drug targets for pathogens.
Recent Developments in Drug Discovery for Leishmaniasis and Human African Trypanosomiasis
The disease history and parasite biology is described followed by a summary of the currently available treatments and, finally, review reports of novel small molecules with antileishmanial activity.
Leishmania major activates IL-1 alpha expression in macrophages through a MyD88-dependent pathway.
- T. Hawn, A. Ozinsky, D. Underhill, F. Buckner, S. Akira, A. Aderem
- Biology, MedicineMicrobes and infection
Observations indicate that Leishmania major stimulates IL-1 alpha promoter activity and mRNA expression in macrophages through MyD88-dependent pathways, however, additional anti-inflammatory pathways must also be activated which downregulate transcription and ultimately inhibit translation of the IL- 1 alpha protein.
Identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice.
This study provides the first proof of concept that DH ODH inhibitors can suppress Plasmodium growth in vivo, validating DHODH as a new target for antimalarial chemotherapy.
Lead optimization of aryl and aralkyl amine-based triazolopyrimidine inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with antimalarial activity in mice.
Systematic efforts to optimize the aromatic functionality with the goal of improving potency and in vivo properties of compounds from the triazolopyrimidine-based Plasmodium falciparum dihydroorotate dehydrogenase-based series led to the identification of two new substituted aniline moieties.