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Pharmacophore modeling and virtual screening for designing potential PLK1 inhibitors.
Bioorg Med Chem Lett. 2008 Sep 15; 18(18):4972-7.BM

Abstract

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+Show Affiliations

Wang HY
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Chengdu, Sichuan 610041, China.
Cao ZX
No affiliation info available
Li LL
No affiliation info available
Jiang PD
No affiliation info available
Zhao YL
No affiliation info available
Luo SD
No affiliation info available
Yang L
No affiliation info available
Wei YQ
No affiliation info available
Yang SY
No affiliation info available

MeSH

AlgorithmsCell Cycle ProteinsDrug DesignDrug Evaluation, PreclinicalHeterocyclic CompoundsInhibitory Concentration 50Models, MolecularMolecular StructureProtein-Serine-Threonine KinasesProto-Oncogene ProteinsStructure-Activity Relationship

Pub Type(s)

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

Language

eng

PubMed ID

18762425

Citation

Wang, Hui-Yuan, et al. "Pharmacophore Modeling and Virtual Screening for Designing Potential PLK1 Inhibitors." Bioorganic & Medicinal Chemistry Letters, vol. 18, no. 18, 2008, pp. 4972-7.
Wang HY, Cao ZX, Li LL, et al. Pharmacophore modeling and virtual screening for designing potential PLK1 inhibitors. Bioorg Med Chem Lett. 2008;18(18):4972-7.
Wang, H. Y., Cao, Z. X., Li, L. L., Jiang, P. D., Zhao, Y. L., Luo, S. D., Yang, L., Wei, Y. Q., & Yang, S. Y. (2008). Pharmacophore modeling and virtual screening for designing potential PLK1 inhibitors. Bioorganic & Medicinal Chemistry Letters, 18(18), 4972-7. https://doi.org/10.1016/j.bmcl.2008.08.033
Wang HY, et al. Pharmacophore Modeling and Virtual Screening for Designing Potential PLK1 Inhibitors. Bioorg Med Chem Lett. 2008 Sep 15;18(18):4972-7. PubMed PMID: 18762425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacophore modeling and virtual screening for designing potential PLK1 inhibitors. AU - Wang,Hui-Yuan, AU - Cao,Zhi-Xing, AU - Li,Lin-Li, AU - Jiang,Pei-Du, AU - Zhao,Ying-Lan, AU - Luo,Shi-Dong, AU - Yang,Li, AU - Wei,Yu-Quan, AU - Yang,Sheng-Yong, Y1 - 2008/08/14/ PY - 2008/03/22/received PY - 2008/07/24/revised PY - 2008/08/09/accepted PY - 2008/9/3/pubmed PY - 2008/10/15/medline PY - 2008/9/3/entrez SP - 4972 EP - 7 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 18 IS - 18 N2 - 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. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/18762425/Pharmacophore_modeling_and_virtual_screening_for_designing_potential_PLK1_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(08)00955-4 DB - PRIME DP - Unbound Medicine ER -