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. 2009 Jul;37(Web Server issue):W504-9.
doi: 10.1093/nar/gkp324. Epub 2009 May 8.

wwLigCSRre: A 3D Ligand-Based Server for Hit Identification and Optimization

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Free PMC article

wwLigCSRre: A 3D Ligand-Based Server for Hit Identification and Optimization

O Sperandio et al. Nucleic Acids Res. .
Free PMC article

Abstract

The wwLigCSRre web server performs ligand-based screening using a 3D molecular similarity engine. Its aim is to provide an online versatile facility to assist the exploration of the chemical similarity of families of compounds, or to propose some scaffold hopping from a query compound. The service allows the user to screen several chemically diversified focused banks, such as Kinase-, CNS-, GPCR-, Ion-channel-, Antibacterial-, Anticancer- and Analgesic-focused libraries. The server also provides the possibility to screen the DrugBank and DSSTOX/Carcinogenic compounds databases. User banks can also been downloaded. The 3D similarity search combines both geometrical (3D) and physicochemical information. Starting from one 3D ligand molecule as query, the screening of such databases can lead to unraveled compound scaffold as hits or help to optimize previously identified hit molecules in a SAR (Structure activity relationship) project. wwLigCSRre can be accessed at http://bioserv.rpbs.univ-paris-diderot.fr/wwLigCSRre.html.

Figures

Figure 1.
Figure 1.
Z-score distributions for active and unrelated compounds. For active compounds, the data plotted corresponds to 47 compounds actives on cyclin-dependent kinase 2 (CDK2), neuraminidase, RNAse, coagulation factor Xa and thymidine kinase. Unrelated compounds correspond to the ChemBridge diversity set (http://www.chembridge.com/), ADME/tox filtered (38 000 compounds).
Figure 2.
Figure 2.
Superimposition of SAR results on IGF-1R.
Figure 3.
Figure 3.
A wwLigCSR run carried out using a Purine bioisostere ligand as the query (a) detected a molecule hit (b) within the Aurora Fine Chemicals Kinase focused library and proposed the corresponding superimposition (c) with a z-score of 2.3.
Figure 4.
Figure 4.
wwLigCSR run on CDK2. 1E9H ligand was used as the query (a) and three known CDK2 inhibitors were correctly detected and superimposed onto the query molecule (b), with respective z-scores of 3.353 (c), 2.708 (d) and 1.740 (e).

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