JQAD1

**JQAD1** is a potent, selective proteolysis-targeting chimera (PROTAC) degrader of the histone acetyltransferase **EP300** (also known as p300), with a DC\u2085\u2080 of \u226431.6 nM in neuroblastoma cell lines. It consists of the EP300 inhibitor **A485** covalently linked via a 12-carbon linker to a cereblon (CRBN) E3 ubiquitin ligase ligand, enabling proteasome-dependent degradation of EP300 while sparing the paralog **CBP** at effective concentrations. JQAD1 suppresses **H3K27ac** levels, downregulates oncogenes like **MYCN** and **CRC**, induces apoptosis in neuroblastoma cells, and inhibits tumor growth in Kelly cell xenografts in NSG mice (40 mg/kg i.p.). Developed as a research tool by researchers including Adam Durbin at St. Jude Children's Research Hospital and Dana-Farber, it highlights EP300 as a synthetic lethal target in **MYCN**-amplified neuroblastoma.[1][2][3][6][14]