Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. Although many high-risk neuroblastoma patients respond to conventional radiation and chemotherapy, only half survive and many continue to suffer from significant toxicities. Novel therapeutics are desperately needed for this disease, especially target specific therapies that will reduce off-target toxicity. Here, we plan to develop an effective strategy for NB by targeting a novel oncoprotein, EP300, which we identified as a dependency in NB. Through our combinatorial chemistry and chemical biology approach, we developed a novel bifunctional molecule JQ-AD1 that can selectively delete EP300 while leaving intact CBP, a close family member of EP300 that is important for normal tissue, but not for NB. Thus, our degrader molecule can stop the growth of neuroblastoma cancer cells while causing little to no toxicity to normal tissues.