title: Discovery of a class of novel tankyrase inhibitors that bind to both the nicotinamide pocket and the induced pocket.
abstract: Potent and selective inhibitors of tankyrases have recently been characterized to bind to an induced pocket. Here we report the identification of a novel potent and selective tankyrase inhibitor that binds to both the nicotinamide pocket and the induced pocket. The crystal structure of human TNKS1 in complex with this "dual-binder" provides a molecular basis for their strong and specific interactions and suggests clues for the further development of tankyrase inhibitors.
authors: Department of Medicinal Chemistry, Amgen Inc., 360 Binney Street, Cambridge, Massachusetts 02142, USA.
authors: Howard
authors: H
authors: Bregman
authors: Hakan
authors: H
authors: Gunaydin
authors: Yan
authors: Y
authors: Gu
authors: Steve
authors: S
authors: Schneider
authors: Cindy
authors: C
authors: Wilson
authors: Erin F
authors: EF
authors: DiMauro
authors: Xin
authors: X
authors: Huang
mesh_terms: D001665:Binding Sites; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D009536:Niacinamide / Q000737:chemistry*; D038501:Tankyrases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D009536:Niacinamide; D038501:Tankyrases; C418109:TNKS protein, human