Discovery of α7-Nicotinic Receptor Ligands by Virtual Screening of the Chemical Universe Database GDB-13
Autor: | Lorenz C. Blum, Milena Mayer, Sonia Bertrand, Jean-Louis Reymond, Daniel Bertrand, Ruud van Deursen, Justus J. Bürgi |
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Rok vydání: | 2011 |
Předmět: |
Databases
Factual alpha7 Nicotinic Acetylcholine Receptor Xenopus General Chemical Engineering Gene Expression Receptors Nicotinic Library and Information Sciences Ligands computer.software_genre 01 natural sciences Small Molecule Libraries Nicotine 03 medical and health sciences Drug Discovery medicine Animals Humans 030304 developmental biology 0303 health sciences Web browser Virtual screening Database Chemistry Ligand Molecular Motor Proteins General Chemistry chEMBL 0104 chemical sciences 3. Good health Computer Science Applications 010404 medicinal & biomolecular chemistry Nicotinic agonist α7 nicotinic receptor Chemical stability computer medicine.drug |
Zdroj: | J. Chem. Inf. Model |
ISSN: | 1549-960X 1549-9596 |
DOI: | 10.1021/ci200410u |
Popis: | The chemical universe database GDB-13 enumerates 977 million organic molecules up to 13 atoms of C, N, O, Cl, and S that are virtually possible following simple rules for chemical stability and synthetic feasibility. Analogs of nicotine were identified in GDB-13 using the city-block distance in MQN-space (CBD(MQN)) as a similarity measure, combined with a restriction eliminating problematic structural elements. The search was carried out with a Web browser available at www.gdb.unibe.ch . This virtual screening procedure selected 31 504 analogs of nicotine from GDB-13, from which 48 were known nicotinic ligands reported in Chembl. An additional 60 virtual screening hits were purchased and tested for modulation of the acetylcholine signal at the human α7 nAChR expressed in Xenopus oocytes, which led to the identification of three previously unknown inhibitors. These experiments demonstrate for the first time the use of GDB-13 for ligand discovery. |
Databáze: | OpenAIRE |
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