title: Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors.
abstract: Dipeptidyl peptidase IV (DPP-4) inhibitors have been shown to enhance GLP-1 levels and thereby improve hyperglycemia in type II diabetes. From a small fragment hit, using structure-based design, we have discovered a new class of non-covalent, potent and selective DPP-4 inhibitors.
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, USA. blam@takedasd.com
authors.forename: Betty
authors.initials: B
authors.lastname: Lam
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Stafford
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Skene
authors.forename: Lihong
authors.initials: L
authors.lastname: Shi
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Gwaltney
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011744:Pyrimidinones