表观遗传学（epigenetics）是指在基因的DNA序列没有发生改变的情况下，基因表达发生了可遗传的改变。组蛋白乙酰化是最常见的表观遗传修饰，在正常细胞过程的调控中（比如细胞分化、增殖、血管生成和凋亡），起到了十分重要的作用。组蛋白乙酰化水平由组蛋白乙酰化酶（HAT）和组蛋白去乙酰化酶（HDAC） 调节。近年来通过调控组蛋白乙酰化水平来治疗疾病且进入临床研究阶段的都是HDAC抑制剂，但基于组蛋白乙酰化酶（HAT）的药物研发还是一片空白，其发展缓慢的主要原因之一就是目前仍没有高效、高选择性以及类药性好的小分子抑制剂。.本项目以组蛋白乙酰化酶p300/CBP为靶点，运用虚拟筛选和高通量筛选，对获得的化合物进行分子以及细胞水平的确证，并结合药物化学进行结构优化，以期获得类药性较好的p300/CBP小分子候选化合物。总之，本研究项目具有明显原创性和探索性，具有较强的理论意义和应用潜力。

Epigenetics is classically defined as the reversible changes in gene expression that do not result from changing DNA sequences. Histone acetylation is the most common epigenetics modifications, playing important roles in the regulation of normal cellular processes such as cell differentiation, proliferation, angiogenesis, and apoptosis. The level of acetylation of histones and nonhistone proteins is governed by two antagonistic families of enzymes: histone deacetylases (HDACs) and histone acetyltransferases (HATs). Although there are several HDAC inhibitors have been developed as market drugs, there is no any HAT inhibitor entering into the clinical trial. Therefore, the development of HAT inhibitor with good drug-like properties is highly desirable..In this project, several small molecule inhibitors with good drug-like properties targeting the histone acetyltransferase p300/CBP will be developed by utilizing the HTS and virtual screening, followed by structure optimization. In summary, this original and novel research has great potential in many applications.