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Pharmacophore modelling and virtual screening for identification of new Aurora-A kinase inhibitors.
Chem Biol Drug Des. 2008 Jun; 71(6):533-9.CB

Abstract

Aurora-A has been identified as one of the most attractive targets for cancer therapy and a considerable number of Aurora-A inhibitors have been reported recently. In order to clarify the essential structure-activity relationship for the known Aurora-A inhibitors as well as identify new lead compounds against Aurora-A, 3D pharmacophore models were developed based on the known inhibitors. The best hypothesis, Hypo1, was used to screen molecular structural databases, including Specs and China Natural Products Database for potential lead compounds. The hit compounds were subsequently subjected to filtering by Lipinski's rules and docking study to refine the retrieved hits and as a result to reduce the rate of false positive. Finally, 39 compounds were purchased for further in vitro assay against several human tumour cell lines including A549, MCF-7, HepG2 and PC-3, in which Aurora-A is overexpressed. Two compounds show very low micromolar inhibition potency against some of these tumour cells. And they have been selected for further investigation.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Deng XQ
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, China.
Wang HY
No affiliation info available
Zhao YL
No affiliation info available
Xiang ML
No affiliation info available
Jiang PD
No affiliation info available
Cao ZX
No affiliation info available
Zheng YZ
No affiliation info available
Luo SD
No affiliation info available
Yu LT
No affiliation info available
Wei YQ
No affiliation info available
Yang SY
No affiliation info available

MeSH

Antineoplastic AgentsAurora KinasesCell Line, TumorComputational BiologyDrug Evaluation, PreclinicalEnzyme InhibitorsHumansModels, MolecularProtein Serine-Threonine Kinases

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18410307

Citation

Deng, Xiao-Qiang, et al. "Pharmacophore Modelling and Virtual Screening for Identification of New Aurora-A Kinase Inhibitors." Chemical Biology & Drug Design, vol. 71, no. 6, 2008, pp. 533-9.
Deng XQ, Wang HY, Zhao YL, et al. Pharmacophore modelling and virtual screening for identification of new Aurora-A kinase inhibitors. Chem Biol Drug Des. 2008;71(6):533-9.
Deng, X. Q., Wang, H. Y., Zhao, Y. L., Xiang, M. L., Jiang, P. D., Cao, Z. X., Zheng, Y. Z., Luo, S. D., Yu, L. T., Wei, Y. Q., & Yang, S. Y. (2008). Pharmacophore modelling and virtual screening for identification of new Aurora-A kinase inhibitors. Chemical Biology & Drug Design, 71(6), 533-9. https://doi.org/10.1111/j.1747-0285.2008.00663.x
Deng XQ, et al. Pharmacophore Modelling and Virtual Screening for Identification of New Aurora-A Kinase Inhibitors. Chem Biol Drug Des. 2008;71(6):533-9. PubMed PMID: 18410307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacophore modelling and virtual screening for identification of new Aurora-A kinase inhibitors. AU - Deng,Xiao-Qiang, AU - Wang,Hui-Yuan, AU - Zhao,Ying-Lan, AU - Xiang,Ming-Li, AU - Jiang,Pei-Du, AU - Cao,Zhi-Xing, AU - Zheng,Yu-Zhu, AU - Luo,Shi-Dong, AU - Yu,Luo-Ting, AU - Wei,Yu-Quan, AU - Yang,Sheng-Yong, Y1 - 2008/04/10/ PY - 2008/4/16/pubmed PY - 2008/7/23/medline PY - 2008/4/16/entrez SP - 533 EP - 9 JF - Chemical biology & drug design JO - Chem Biol Drug Des VL - 71 IS - 6 N2 - Aurora-A has been identified as one of the most attractive targets for cancer therapy and a considerable number of Aurora-A inhibitors have been reported recently. In order to clarify the essential structure-activity relationship for the known Aurora-A inhibitors as well as identify new lead compounds against Aurora-A, 3D pharmacophore models were developed based on the known inhibitors. The best hypothesis, Hypo1, was used to screen molecular structural databases, including Specs and China Natural Products Database for potential lead compounds. The hit compounds were subsequently subjected to filtering by Lipinski's rules and docking study to refine the retrieved hits and as a result to reduce the rate of false positive. Finally, 39 compounds were purchased for further in vitro assay against several human tumour cell lines including A549, MCF-7, HepG2 and PC-3, in which Aurora-A is overexpressed. Two compounds show very low micromolar inhibition potency against some of these tumour cells. And they have been selected for further investigation. SN - 1747-0285 UR - https://www.unboundmedicine.com/medline/citation/18410307/Pharmacophore_modelling_and_virtual_screening_for_identification_of_new_Aurora_A_kinase_inhibitors_ DB - PRIME DP - Unbound Medicine ER -