The National Institute of Neurological Disorders and Stroke (NINDS) awarded a $1,830,581 Project Grant (CFDA 93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders) to The Johns Hopkins University to conduct in-depth characterization of the mode of action of a new macrocycle compound called "RAPIREON." The project aims to use biochemical and structural biology approaches to better understand how RAPIREON acts as a "molecular glue" to selectively activate the nuclease activity of the IRE1 protein, a key component of the unfolded protein response pathway. This research could provide insights into potential therapeutic interventions for neurodegenerative diseases. The project runs from September 2024 through August 2027 and will build on preliminary low-resolution cryo-EM and high-resolution X-ray crystal structure data to refine the structural model of the RAPIREON-IRE1 complex to a resolution of 2.5 Angstroms or better.
Generated 3/4/25, 2:23 AM