Aaron David Schimmer

Allosteric inhibition of human mitochondrial ClpP by hijacking the dordaviprone (ONC201) binding site

ClpP protease maintains proteostasis in human mitochondria and is overexpressed in cancers such as acute myeloid leukemia (AML). While activators such as dordaviprone (ONC201) have reached the clinic, the development of ClpP inhibitors has been hampered by paradoxical activation...