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Presented By: Center for the Discovery of New Medicines - CDNM

Drug Discovery Seminar - "Next-Generation Dihydrofolate Reductase Inhibitors for the Treatment of Neglected Parasitic Infections"

Stephen Thomas, Ph.D.

Neglected parasitic infections represent a sub-class of infectious diseases with significant morbidity and mortality, but remarkably little progress over the past 50 years in development of drugs to treat such conditions. Because these diseases are found primarily in poor and developing countries, traditional incentives have been insufficient to encourage pharmaceutical development of new and innovative drug therapies. Although generally rare in the United States, globalization has increased the impact these diseases have on the health of Americans and the FDA has more recently introduced legislation to stimulate the development of new treatments. Turing Pharmaceuticals has applied modern drug discovery approaches to clinically validated therapeutic paradigms in efforts to identify next-generation therapies for neglected parasitic infections. One such paradigm, dihydrofolate reductase (DHFR) inhibition, has proven highly efficacious against multiple parasitic disease models. However, achieving a high degree of selectivity for parasite DHFR over its human ortholog has proven difficult, hindering development due to concerns regarding host toxicity. Using structure-based drug design and proprietary in silico screening methodology, Turing has identified some of the most potent and selective parasite DHFR inhibitors known to date and demonstrated their activity in relevant pharmacology models. These small molecules collectively represent a promising platform advancing toward clinical development for the treatment of neglected parasitic infections.

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