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Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies

Kinase insert domain receptor (KDR) inhibitors have been proved to be very effective anticancer agents. Molecular docking, 3D-QSAR methods, CoMFA and CoMSIA were performed on pyrrolo[3,2-d]pyrimidine derivatives as non-ATP competitive KDR inhibitors (type II). The bioactive conformation was explored...

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Autores principales: Wu, Xiao-Yun, Chen, Wen-Hua, Wu, Shu-Guang, Tian, Yuan-Xin, Zhang, Jia-Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292029/
https://www.ncbi.nlm.nih.gov/pubmed/22408460
http://dx.doi.org/10.3390/ijms13022387
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author Wu, Xiao-Yun
Chen, Wen-Hua
Wu, Shu-Guang
Tian, Yuan-Xin
Zhang, Jia-Jie
author_facet Wu, Xiao-Yun
Chen, Wen-Hua
Wu, Shu-Guang
Tian, Yuan-Xin
Zhang, Jia-Jie
author_sort Wu, Xiao-Yun
collection PubMed
description Kinase insert domain receptor (KDR) inhibitors have been proved to be very effective anticancer agents. Molecular docking, 3D-QSAR methods, CoMFA and CoMSIA were performed on pyrrolo[3,2-d]pyrimidine derivatives as non-ATP competitive KDR inhibitors (type II). The bioactive conformation was explored by docking one potent compound 20 into the active site of KDR in its DFG-out inactive conformation. The constructed CoMFA and CoMSIA models produced statistically significant results with the cross-validated correlation coefficients q(2) of 0.542 and 0.552, non-cross-validated correlation coefficients r(2) of 0.912 and 0.955, and predicted correction coefficients r(2)(pred) of 0.913 and 0.897, respectively. These results ensure the CoMFA and CoMSIA models as a tool to guide the design of a series of new potent KDR inhibitors.
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spelling pubmed-32920292012-03-09 Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies Wu, Xiao-Yun Chen, Wen-Hua Wu, Shu-Guang Tian, Yuan-Xin Zhang, Jia-Jie Int J Mol Sci Article Kinase insert domain receptor (KDR) inhibitors have been proved to be very effective anticancer agents. Molecular docking, 3D-QSAR methods, CoMFA and CoMSIA were performed on pyrrolo[3,2-d]pyrimidine derivatives as non-ATP competitive KDR inhibitors (type II). The bioactive conformation was explored by docking one potent compound 20 into the active site of KDR in its DFG-out inactive conformation. The constructed CoMFA and CoMSIA models produced statistically significant results with the cross-validated correlation coefficients q(2) of 0.542 and 0.552, non-cross-validated correlation coefficients r(2) of 0.912 and 0.955, and predicted correction coefficients r(2)(pred) of 0.913 and 0.897, respectively. These results ensure the CoMFA and CoMSIA models as a tool to guide the design of a series of new potent KDR inhibitors. Molecular Diversity Preservation International (MDPI) 2012-02-22 /pmc/articles/PMC3292029/ /pubmed/22408460 http://dx.doi.org/10.3390/ijms13022387 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Wu, Xiao-Yun
Chen, Wen-Hua
Wu, Shu-Guang
Tian, Yuan-Xin
Zhang, Jia-Jie
Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies
title Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies
title_full Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies
title_fullStr Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies
title_full_unstemmed Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies
title_short Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies
title_sort pyrrolo[3,2-d]pyrimidine derivatives as type ii kinase insert domain receptor (kdr) inhibitors: comfa and comsia studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292029/
https://www.ncbi.nlm.nih.gov/pubmed/22408460
http://dx.doi.org/10.3390/ijms13022387
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