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Tuesday, August 25 • 4:00pm - 4:20pm
[0177] Discovery and Optimization of Novel Inhibitors of the Mitochondrial Permeability Transition Pore

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The mitochondrial permeability transition pore (mtPTP) is a Ca2+-requiring megachannel that permanently opens under pathological conditions and leads to deregulated release of Ca2+ and mitochondrial dysfunction. For the past couple of decades the mtPTP has been implicitly recognized as a therapeutic target for several deadly diseases such as Alzheimer’s disease, muscular dystrophies, myocardial infarction, stroke, and diabetes. Herein we report the results of a high-throughput screening/chemical optimization approach that led to the discovery of two new chemotypes: (a) diarylisoxazole-3-carboxamides and (b) N-phenylbenzamides, which are first subnanomolar inhibitors of the mtPTP. The therapeutic potential and in vivo efficacy of the most potent analogues were validated in a biologically relevant zebrafish model of collagen VI congenital muscular dystrophies.

ST Lecturers
avatar for Sudeshna Roy

Sudeshna Roy

Postdoctoral Fellow in Medicinal/Organic Chemistry at University North Carolina at Chapel Hill (current), The University of Kansas (past). Advisor Prof. Jeffrey Aubé Ph.D. in Organic Chemistry in 2012. Advisor Prof. C. D. Spilling at University of Missouri-St. Louis. Research Interests... Read More →

Tuesday August 25, 2015 4:00pm - 4:20pm PDT
Girvetz 2119