Selectively targeting EP300 with small molecule inhibitors for neuroblastoma therapy
Mentor Name: Jun Qi
The student’s project with Dr. Jun Qi will be working on optimizing a selective degrader for EP300 as a therapeutic for neuroblastoma, the most common pediatric extracranial solid tumor. The majority of pediatric patients present with neuroblastoma display an exceedingly poor overall survival with significant side effects following multimodal treatment. Recently, the Qi group has identified that neuroblastoma is highly dependent on the function of EP300 but not its paralog, CBP. Thus, selectively targeting EP300 and sparing CBP may inhibit neuroblastoma cell growth while limiting toxicity to normal tissues. The student’s project will research the optimization and validation of JQ-AD1, a selective PROTAC that degrades EP300 but not CBP. The degradation activity of these degraders will be explored in translational preclinical models of neuroblastoma. By the end of this research, a series of degraders that are more potent and selective than JQ-AD1 for EP300 will offer a novel therapeutic strategy for drug development in neuroblastoma, which is desperately needed.
