The discovery of novel HDAC3 inhibitors via virtual screening and in vitro bioassay.
作者： Jie Xia , Huabin Hu , Wenjie Xue , Xiang Simon Wang , Song Wu
DOI: 10.1080/14756366.2018.1437156
关键词: Computational biology 、 Autodock vina 、 Quantitative structure–activity relationship 、 In vitro 、 Bioassay 、 Chemical library 、 Virtual screening 、 Computer science 、 Drug discovery
摘要: AbstractHistone deacetylase 3 (HDAC3) is a potential target for the treatment of human diseases such as cancers, diabetes, chronic inflammation and neurodegenerative diseases. Previously, we proposed virtual screening (VS) pipeline named “Hypo1_FRED_SAHA-3” discovery HDAC3 inhibitors (HDAC3Is) had thoroughly validated it by theoretical calculations. In this study, attempted to explore its practical utility in large-scale VS campaign. To end, used hierarchically screen Specs chemical library. order facilitate compound cherry-picking, then developed knowledge-based pose filter (PF) using our in-house quantitative structure activity relationship- (QSAR-) modelling approach coupled with FRED Autodock Vina. Afterward, purchased tested 11 diverse compounds their inhibitory vitro. The bioassay has identified 2 (Specs ID: AN-979/41971160) HDAC3I (IC50 = 6.1 μM), which proved efficacy our...
sci-hub.se 参考文章(51)
Dan P Christensen, Mattias Dahllöf, Morten Lundh, Daniel N Rasmussen, Mette D Nielsen, Nils Billestrup, Lars G Grunnet, Thomas Mandrup-Poulsen, None, Histone Deacetylase (HDAC) Inhibition as a Novel Treatment for Diabetes Mellitus Molecular Medicine. ,vol. 17, pp. 378- 390 ,(2011) , 10.2119/MOLMED.2011.00021
M. Lundh, T. Galbo, S. S. Poulsen, T. Mandrup-Poulsen, Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in obese diabetic rats. Diabetes, Obesity and Metabolism. ,vol. 17, pp. 703- 707 ,(2015) , 10.1111/DOM.12470
Ulrich Mahlknecht, Dieter Hoelzer, Histone acetylation modifiers in the pathogenesis of malignant disease. Molecular Medicine. ,vol. 6, pp. 623- 644 ,(2000) , 10.1007/BF03402044
Sabbir Khan, Gopabandhu Jena, None, The role of butyrate, a histone deacetylase inhibitor in diabetes mellitus: experimental evidence for therapeutic intervention Epigenomics. ,vol. 7, pp. 669- 680 ,(2015) , 10.2217/EPI.15.20
Jie Xia, Ermias Lemma Tilahun, Eyob Hailu Kebede, Terry-Elinor Reid, Liangren Zhang, Xiang Simon Wang, Comparative modeling and benchmarking data sets for human histone deacetylases and sirtuin families. Journal of Chemical Information and Modeling. ,vol. 55, pp. 374- 388 ,(2015) , 10.1021/CI5005515
Shuxing Zhang, Alexander Golbraikh, Alexander Tropsha, Development of quantitative structure-binding affinity relationship models based on novel geometrical chemical descriptors of the protein-ligand interfaces Journal of Medicinal Chemistry. ,vol. 49, pp. 2713- 2724 ,(2006) , 10.1021/JM050260X
Ricky W. Johnstone, Histone-deacetylase inhibitors: novel drugs for the treatment of cancer Nature Reviews Drug Discovery. ,vol. 1, pp. 287- 299 ,(2002) , 10.1038/NRD772
Danny Hung-Chieh Chou, Edward B. Holson, Florence F. Wagner, Alicia J. Tang, Rebecca L. Maglathlin, Timothy A. Lewis, Stuart L. Schreiber, Bridget K. Wagner, Inhibition of histone deacetylase 3 protects beta cells from cytokine-induced apoptosis Chemistry & Biology. ,vol. 19, pp. 669- 673 ,(2012) , 10.1016/J.CHEMBIOL.2012.05.010
Haiqun Jia, Charles D. Morris, Roy M. Williams, Jeanne F. Loring, Elizabeth A. Thomas, HDAC inhibition imparts beneficial transgenerational effects in Huntington's disease mice via altered DNA and histone methylation Proceedings of the National Academy of Sciences of the United States of America. ,vol. 112, pp. 201415195- ,(2015) , 10.1073/PNAS.1415195112
M. A. Lazar, M. A. Wood, S. C. McQuown, R. M. Barrett, D. P. Matheos, R. J. Post, G. A. Rogge, T. Alenghat, S. E. Mullican, S. Jones, J. R. Rusche, HDAC3 Is a Critical Negative Regulator of Long-Term Memory Formation The Journal of Neuroscience. ,vol. 31, pp. 764- 774 ,(2011) , 10.1523/JNEUROSCI.5052-10.2011