JQAD1 is a potent and selective histone acetyltransferase EP300 degrader (PROTAC®; 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.

JQAD1（0.5或1μM；6-96小时）处理早期依时间依赖性引发Sub-G1峰的诱导，表明Kelly和NGP细胞发生了凋亡。JQAD1（1μM；12-36小时）诱导Kelly NB细胞凋亡。JQAD1（0.5μM；24小时）处理的细胞显示出BH3效应分子BIM、BID和PUMA，促凋亡介质BAX及其抑制剂BCL2和MCL1的上调。JQAD1（0.5和1μM；24小时）抑制MYCN表达。JQAD1（0.5μM；24小时）导致染色质上H3K27ac的缺失。JQAD1（1.2nM-20μM；5天）在癌细胞系中显示出广泛的CRBN依赖的抗肿瘤活性。JQAD1依时间依赖性诱导EP300的降解，最早在16小时[1]。

JQAD1（40 mg/kg; i.p.; 每日一次，连续21天）在NSG小鼠中抑制了植入Kelly NB细胞的肿瘤生长[1]。