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As reported by Therapeutics Daily, January 16, 2009.

New Enzyme Research Study Findings Reported from University of Connecticut

According to recent research published in the Journal of Medicinal Chemistry, "Cryptosporidiosis is an emerging infectious disease that can be life-threatening in ail immune-compromised individual and causes gastrointestinal distress lasting up to 2 weeks in an immune-competent individual. There are few therapeutics available for effectively treating this disease."

"We have been exploring dihydrofolate reductase (DHFR) as a potential target in Cryptosporidium. On the basis of the structure of the DHFR enzyme from C. hominis, we have developed a novel scaffold that led to the discovery of potent (38 nM) and efficient inhibitors of this enzyme. Recently, we have advanced these inhibitors to the next stage of development," wrote D.B. Bolstad and colleagues, University of Connecticut.

The researchers concluded: "Using the Structures of both the protozoal and human enzymes. we have developed inhibitors with nanomolar potency (1.1 nM) against the pathogenic enzyme and high levels (1273-fold) of selectivity over the human enzyme."

Bolstad and colleagues published their study in the Journal of Medicinal Chemistry (Structure-Based Approach to the Development of Potent and Selective Inhibitors of Dihydrofolate Reductase from Cryptosporidium. Journal of Medicinal Chemistry, 2008;51(21):6839-6852).

For additional information, contact A.C. Anderson, University of Connecticut, Department of Pharmaceutical Science, Storrs, Connecticut, 06269.