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Substructure-Based Virtual Screening for Adenosine A2A Receptor Ligands
- Source :
- ChemMedChem. 6:2302-2311
- Publication Year :
- 2011
- Publisher :
- Wiley, 2011.
-
Abstract
- A virtual ligand-based screening approach was designed and evaluated for the discovery of new A(2A) adenosine receptor (AR) ligands. For comparison and evaluation, the procedures from a recently published virtual screening study that used the A(2A) AR X-ray crystal structure for the target-based discovery of new A(2A) ligands were largely followed. Several screening models were constructed by deriving the distinguishing structural features from selected sets of A(2A) AR antagonists, so-called frequent substructure mining. The best model in statistical terms was subsequently applied to large-scale virtual screens of a commercial vendor library. This resulted in the selection of 36 candidates for acquisition and testing. Of the selected candidates, eight compounds significantly inhibited radioligand binding at A(2A) AR (>30%) at 10 μM, corresponding to a "hit rate" of 22%. This hit rate is quite similar to that of the referenced target-based virtual screening study, while both approaches yield new, non-overlapping sets of ligands.
- Subjects :
- Pharmacology
Virtual screening
Receptor, Adenosine A2A
Drug discovery
Chemistry
Ligand
Organic Chemistry
Drug Evaluation, Preclinical
Adenosine A2A receptor
Computational biology
Ligands
Biochemistry
Combinatorial chemistry
Adenosine A2 Receptor Antagonists
Structure-Activity Relationship
Radioligand binding
Drug Discovery
Hit rate
Humans
Molecular Medicine
Substructure
General Pharmacology, Toxicology and Pharmaceutics
Software
Protein Binding
Subjects
Details
- ISSN :
- 18607179
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- ChemMedChem
- Accession number :
- edsair.doi.dedup.....add05007f6ec49b0706c9227b109c7ce