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Int. J. Mol. Sci. 2012, 13(12), 17185-17209; doi:10.3390/ijms131217185
Article

Virtual Screening of Specific Insulin-Like Growth Factor 1 Receptor (IGF1R) Inhibitors from the National Cancer Institute (NCI) Molecular Database

1
, 1,* , 1,* , 1
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 and 2,*
1 National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China 2 Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China
* Authors to whom correspondence should be addressed.
Received: 10 October 2012 / Revised: 21 November 2012 / Accepted: 11 December 2012 / Published: 14 December 2012
(This article belongs to the Section Bioinorganic Chemistry)
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Abstract

Insulin-like growth factor 1 receptor (IGF1R) is an attractive drug target for cancer therapy and research on IGF1R inhibitors has had success in clinical trials. A particular challenge in the development of specific IGF1R inhibitors is interference from insulin receptor (IR), which has a nearly identical sequence. A few potent inhibitors that are selective for IGF1R have been discovered experimentally with the aid of computational methods. However, studies on the rapid identification of IGF1R-selective inhibitors using virtual screening and confidence-level inspections of ligands that show different interactions with IGF1R and IR in docking analysis are rare. In this study, we established virtual screening and binding-mode prediction workflows based on benchmark results of IGF1R and several kinase receptors with IGF1R-like structures. We used comprehensive analysis of the known complexes of IGF1R and IR with their binding ligands to screen specific IGF1R inhibitors. Using these workflows, 17 of 139,735 compounds in the NCI (National Cancer Institute) database were identified as potential specific inhibitors of IGF1R. Calculations of the potential of mean force (PMF) with GROMACS were further conducted for three of the identified compounds to assess their binding affinity differences towards IGF1R and IR.
Keywords: IGF1R; IR; virtual screening; binding mode prediction; selective inhibition IGF1R; IR; virtual screening; binding mode prediction; selective inhibition
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Fan, C.; Huang, Y.-X.; Bao, Y.-L.; Sun, L.-G.; Wu, Y.; Yu, C.-L.; Zhang, Y.; Song, Z.-B.; Zheng, L.-H.; Sun, Y.; Wang, G.-N.; Li, Y.-X. Virtual Screening of Specific Insulin-Like Growth Factor 1 Receptor (IGF1R) Inhibitors from the National Cancer Institute (NCI) Molecular Database. Int. J. Mol. Sci. 2012, 13, 17185-17209.

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