P300是CBP/P300 家族中一种重要的组蛋白乙酰转移酶。研究表明，P300在肝癌、前列腺癌、小细胞肺癌等多种恶性肿瘤都存在高表达，是肿瘤治疗的潜在靶点，目前仍没有针对该靶点的理想抑制剂。申请人通过虚拟筛选及活性测试，获得了一个P300小分子抑制剂苗头化合物，但其与蛋白的作用模式还有待确证，选择性与活性还有待提高。本项目拟针对该苗头化合物进行进一步的结构优化并研究其构效关系，以期获得高选择性高活性的小分子抑制剂。通过小分子蛋白复合物晶体的解析，将有助于小分子作用模式的理解，并为结构优化提供理论指导依据。

P300 is an important histone acetyltransferase in the CBP / P300 family. Studies have shown that P300 are highly expressed in liver cancer, prostate cancer, small cell lung cancer and other malignant tumors. It is a potential target for cancer treatment, but there is no ideal inhibitor reported till now. Through the virtual screening and activity test, applicants obtained a hit compound, but the action mode between the small molecule and P300 needs to be validated while its selectivity and activity needs to be improved. This project aims to further optimize the structure of the compound and study its structure-activity relationship in order to obtain high selectivity and activity of small molecule inhibitors. The understanding of the action mode between the small molecule and P300 by the analysis of the crystal structure of the complex can provide the theoretical guidance for the structural optimization.