Discovery of a class of novel tankyrase inhibitors that bind to both the nicotinamide pocket and the induced pocket

J Med Chem. 2013 Feb 14;56(3):1341-5. doi: 10.1021/jm301607v. Epub 2013 Jan 23.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Drug Discovery
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Niacinamide / chemistry*
  • Tankyrases / antagonists & inhibitors*


  • Enzyme Inhibitors
  • Niacinamide
  • Tankyrases
  • TNKS protein, human