JQAD1

Description: JQAD1 is a potent and selective histone acetyltransferase EP300 degrader (PROTAC(R), DC50= 31.6 nM), comprises an EP300 inhibitor, A485, joined by a linker to a cereblon E3 ligase ligand. JQAD1 brings about degradation of EP300 in neuroblastoma cell lines in a proteasome-dependent manner. JQAD1 suppresses both H3K27ac and EP300 expression levels and induces apoptosis. JQAD1 suppresses tumors growth in NSG mice xenografted with Kelly cells. CRC and MYCN genes are downregulated in tumors treated with JQAD1. JQAD1 exhibits no significant effect on coactivator CBP at concentrations inducing EP300 degradation. Target: Epigenetic Reader Domain, PROTACs. Smiles: O=C1[C@@]2(C=3C(CC2)=CC(NC(CCCCCCCCCC CNC=4C=C5C(=CC4)C(=O)N(C5=O)C6C(=O)NC(=O)CC6)=O)=CC3)OC(=O)N1CC(N(CC7=CC=C(F)C=C7)[C@H](C(F)(F)F)C)=O. References: Durbin et al (2021) EP300 selectively controls the enhancer landscape of MYCN-amplified neuroblastoma. Cancer Discov.