Antifungal drug discovery: something old and something new

[...]our laboratory used the AK assay in a screen of mechanistically distinct protein kinase inhibitors designed to identify fungilytic inhibitors of the cell wall integrity kinase signaling cascade, a stress response pathway conserved across pathogenic fungi. Perspective An interesting theme shared...

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Bibliographic Details
Published in:PLoS pathogens 2012-09, Vol.8 (9), p.e1002870-e1002870
Main Authors: Butts, Arielle, Krysan, Damian J
Format: Article
Language:English
Subjects:
Antifungal agents
Antifungal Agents - chemical synthesis
Antifungal Agents - isolation & purification
Biology
Cell Wall - drug effects
Chemistry
Drug Discovery - methods
Drug Discovery - trends
Drug Repositioning
Fungi
Health Services Needs and Demand
Humans
Kinases
Medical research
Medicine
Medicine, Experimental
Microbial Sensitivity Tests - methods
Models, Biological
Molecular Targeted Therapy - methods
Molecular Targeted Therapy - trends
Mortality
Mycoses - drug therapy
Pearls
Pharmaceutical industry
Proteins
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Description
Summary:[...]our laboratory used the AK assay in a screen of mechanistically distinct protein kinase inhibitors designed to identify fungilytic inhibitors of the cell wall integrity kinase signaling cascade, a stress response pathway conserved across pathogenic fungi. Perspective An interesting theme shared by the new antifungal targets described above is that many target proteins with orthologs in human cells. Since the targets of most current antifungal drugs are unique to fungi, this represents a significant conceptual evolution that seeks to exploit the sometimes subtle differences in protein structure between host and pathogen to identify molecules with selectivity for the fungal protein and, thereby, acceptable toxicity toward the host.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1002870