CBC Colloquium Series: "Targeting dihydroorotate dehydrogenase for the treatment of malaria"

When

3:30 – 4:30 p.m., Feb. 16, 2023
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Margaret Phillips

Abstract: Malaria is one of the most widespread and ancient infectious diseases. It puts at risk 50% of the world’s population, infecting over 200 million people yearly, and leading to ~0.6 million deaths, most occurring in African in children under five. Malaria is controlled primarily through drug therapy, however drug resistance has compromised most drugs that have been used to combat the disease.  Thus new drugs are needed to ensure that patients will have available treatments for this deadly disease.  Our group identified and validated dihydroorotate dehydrogenase (DHODH) as a new drug target for the treatment of malaria.  We identified and optimized DHODH inhibitors from two different chemical series, that are potent and selective for the malaria enzyme over the human enzyme.  We identified a clinical development candidate from a triazolopyrimidine series that was shown to be effective at both treatment and chemoprevention of malaria in humans. More recently we have identified additional possible candidates from a pyrrole-based series.   My lecture will cover the program spanning from initial hit identification, through lead optimization, and summary of the clinical findings.

Presenter

Dr. Margaret Phillips Professor and Chair, Biochemistry and Pharmacology, UT Southwestern Medical Center

Host

Dr. Marie-Pierre Hasne