title: In silico fragment-based discovery of DPP-IV S1 pocket binders.
abstract: Dipeptidyl peptidase IV is a clinically validated target for type-2 diabetes and belongs to a family of peptidases with a quite unique post-proline cleavage specificity. Known inhibitors contain a limited number of molecular anchors occupying the small prototypical S1 pocket. A virtual screening approach for such S1-binding fragments was carried out using FlexX docking to evaluate its potential to confirm known and find novel compounds. Several low molecular weight inhibitors exhibiting activities in the micromolar range could be identified as starting points for structure-based design.
authors.affiliation: Computational Discovery, Santhera Pharmaceuticals, Im Neuenheimer Feld 518-519, 69120 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rummey
authors.forename: Sonja
authors.initials: S
authors.lastname: Nordhoff
authors.forename: Meinolf
authors.initials: M
authors.lastname: Thiemann
authors.forename: Günther
authors.initials: G
authors.lastname: Metz
mesh_terms: D001665:Binding Sites; D019295:Computational Biology; D018360:Crystallography, X-Ray; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry* / Q000378:metabolism*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008970:Molecular Weight; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4