Acetylation plays a key role in maintaining and balancing cellular regulation and homeostasis. Acetyltransferases are an important class of enzymes which mediate this acetylation process. EP300 is a type 3 major lysine (K) acetyl transferase, and its aberrant activity is implicated in many human diseases. Hence, targeting EP300 mediated acetylation is a necessary step to control the associated diseases. Currently, a few EP300 inhibitors are known, among which curcumin is the most widely investigated molecule. However, due to its instability, chemical aggregation and reactivity, its inhibitory activity against the EP300 acetyltransferase domain is disputable. To address this curcumin problem, different curcumin analogues have been synthesized. These molecules were selected for screening against the EP300 acetyltransferase domain using in silico docking and MD analysis. We have successfully elucidated that the curcumin analogue CNB001 is a potential EP300 inhibitor with good drug-like characteristics.

乙酰化在维持和平衡细胞调节和体内平衡中起关键作用。乙酰基转移酶是介导该乙酰化过程的重要一类酶。EP300是3型主要赖氨酸（K）乙酰转移酶，其异常活性与许多人类疾病有关。因此，靶向EP300介导的乙酰化是控制相关疾病的必要步骤。当前，已知几种EP300抑制剂，其中姜黄素是研究最广泛的分子。然而，由于其不稳定性，化学聚集和反应性，其对EP300乙酰基转移酶结构域的抑制活性是有争议的。为了解决这个姜黄素问题，已经合成了不同的姜黄素类似物。选择这些分子以使用EP300乙酰转移酶结构域进行筛选在计算机对接和MD分析中。我们已经成功地阐明了姜黄素类似物CNB001是具有良好药物样特性的潜在EP300抑制剂。