| Pharmacophore modeling and virtual screening for designing potential PLK1 inhibitors. | |
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MedLine Citation:
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PMID: 18762425 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pharmacophore models of Polo-like kinase-1 (PLK1) inhibitors have been established by using the HipHop and HypoGen algorithms implemented in the Catalyst software package. The best quantitative pharmacophore model, Hypo1, which has the highest correlation coefficient (0.9895), consists of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic feature, and one hydrophobic aliphatic feature. Hypo1 was further validated by test set and cross validation method. Then Hypo1 was used as a 3D query to screen several databases including Specs, NCI, Maybridge, and Chinese Nature Product Database (CNPD). The hit compounds were subsequently subjected to filtering by Lipinski's rule of five and docking study to refine the retrieved hits and as a result to reduce the rate of false positive. Finally, a total of 20 compounds were selected and have been shifted to in vitro and in vivo studies. As far as we know, this is the first report on the pharmacophore modeling even the first publicly reported virtual screening study of PLK1 inhibitors. |
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Authors:
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Hui-Yuan Wang; Zhi-Xing Cao; Lin-Li Li; Pei-Du Jiang; Ying-Lan Zhao; Shi-Dong Luo; Li Yang; Yu-Quan Wei; Sheng-Yong Yang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-14 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 18 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-09-15 Completed Date: 2008-10-14 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 4972-7 Citation Subset: IM |
Affiliation:
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State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Chengdu, Sichuan 610041, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Cell Cycle Proteins / antagonists & inhibitors* Drug Design* Drug Evaluation, Preclinical / methods* Heterocyclic Compounds / chemical synthesis*, chemistry, pharmacology* Inhibitory Concentration 50 Models, Molecular* Molecular Structure Protein-Serine-Threonine Kinases / antagonists & inhibitors* Proto-Oncogene Proteins / antagonists & inhibitors* Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Heterocyclic Compounds; 0/Proto-Oncogene Proteins; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/polo-like kinase 1 |
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