ICG-001 analogs as antileukemia agents: structure-activity relationships and preclinical activity
Aug. 16, 2023
Leukemic cells rely on excessive mitochondrial respiratory and energy metabolism. Therefore, targeting mitochondrial proteases has been proposed as a potential approach to improve therapeutic regimens for acute myeloid leukemia (AML). The mitochondrial caseinolytic protease P (ClpP), located in the mitochondrial matrix, maintains protein quality by mediating the proteolytic hydrolysis of damaged proteins. The chaperone ClpX regulates this hydrolysis and is overexpressed in AML, thus providing a rationale for using ClpP agonists to disrupt AML proliferation.