A prospective cross-screening study on G-protein-coupled receptors: lessons learned in virtual compound library design.
- Sanders, M.P.A.
- Roumen, L.
- Horst, E. van der
- Lane, J.R.
- Vischer, H.F.
- Offenbeek, J. van
- Vries, H. de
- Verhoeven, S.
- Chow, K.Y.
- Verkaar, F.
- Beukers, M.W.
- McGuire, R.
- Leurs, R.
- IJzerman, A.P.
- de Vlieg, J.
- Esch, I.J. de
- Zaman, G.J.
- Klomp, J.P.G.
- Bender, A.
- Graaf, C. de
DOIAbstract
Contains fulltext : 103510.pdf (Publisher’s version ) (Closed access)We present the systematic prospective evaluation of a protein-based and a ligand-based virtual screening platform against a set of three G-protein-coupled receptors (GPCRs): the beta-2 adrenoreceptor (ADRB2), the adenosine A(2A) receptor (AA2AR), and the sphingosine 1-phosphate receptor (S1PR1). Novel bioactive compounds were identified using a consensus scoring procedure combining ligand-based (frequent substructure ranking) and structure-based (Snooker) tools, and all 900 selected compounds were screened against all three receptors. A striking number of ligands showed affinity/activity for GPCRs other than the intended target, which could be partly attr...
Add to ORKG