Department of Organic Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Eur J Med Chem. 2010 May;45(5):1777-91. doi: 10.1016/j.ejmech.2010.01.010. Epub 2010 Jan 28.
A three dimensional (3D) chemical feature based pharmacophore model was developed for selective histone deacetylase 1 (HDAC1) inhibitors, which provides an efficient way to discuss the isoform selectivity of HDAC inhibitors. In contrast to the classical pan-HDAC pharmacophore, two hydrophobic features (HY and HYAr2) were found in the chemical feature based pharmacophore model, which might be responsible for the selectivity of HDAC1 inhibitions. Molecular docking also highlighted the two hydrophobic features, which are located in the internal cavity adjacent to the active site. The results contribute to our understanding of the molecular mechanism underlying the selectivity of HDAC1 inhibitors and suggest a possible target region to design novel selective HDAC1 inhibitors.
针对选择性组蛋白去乙酰化酶 1（HDAC1）抑制剂，建立了一个三维（3D）化学特征药效团模型，为探讨 HDAC 抑制剂的同型选择性提供了有效途径。与经典的泛 HDAC 药效团模型不同，在基于化学特征的药效团模型中发现了两个疏水性特征（HY 和 HYAr2），这可能是 HDAC1 抑制剂选择性的原因。分子对接也突出了这两个位于靠近活性位点的内部腔中的疏水性特征。这些结果有助于我们理解 HDAC1 抑制剂选择性的分子机制，并为设计新型选择性 HDAC1 抑制剂提供了一个可能的靶区。
