Parasite infections affect billions of humans world-wide, yet the current drugs available for the treatment of many parasitic diseases are either inadequate, or compromised by the development of resistance. Validation of a drug target is an important step in the development of new drugs. Target validation encompasses verifying that a target is primarily responsible for the therapeutic activity of a proven drug, or demonstrating the essential nature of a putative drug target in a parasite, and the capacity for selective inhibition of that target in vivo. Selective toxicity may be achieved by taking advantage of unique parasite biology or biochemistry, or by utilizing differences in metabolism or import. The essential nature of a target may be demonstrated by the correlation of the chemical or genetic reduction of target activity with the loss of parasite growth or virulence. Rescue experiments may demonstrate the single nature of a target. Ultimately, a target must be validated in vivo.
Keywords: target validation, parasite metabolism, divergent biology, pyrimethamine, doxp reductoisomerase, pfor, odc, ts-dhfr, rna interference
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