New antimalarial targets: the example of glucose transport.

In order for a novel drug target to attract attention it must be shown to be essential for parasite survival. In addition, it is desirable that a novel target provides some molecular and functional basis for the development of selective inhibitors. In this respect the pathway for transport of glucose to the parasite in Plasmodium falciparum has attracted increasing interest as a target for antimalarial chemotherapy. In particular, the plasmodial hexose transporter, PfHT, known to mediate transport of this essential substrate to the parasite has been a promising candidate for development of inhibitors. The article summarises the steps involved in development of this parasite protein as a drug target. Details of PfHT identification, functional characterisation and its validation as a drug target by using a selective inhibitor are discussed. The potential use of a robust system to screen libraries of compounds in a high-throughput format, in pursuit of an inhibitor of PfHT is also described. In conclusion PfHT represents one example of a rational approach in the drug discovery process to structure-base design of drugs.