Diamond Publications - Search Results

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

One item found (0 items not approved).

Instruments / Technical Area	Publication Details	Published	Actions
I04-Macromolecular Crystallography	Para substituted 2-phenyl-3,4-dihydroquinazolin-4-ones as potent and selective tankyrase inhibitors Teemu Haikarainen , Jarkko Koivunen , Mohit Narwal , Harikanth Venkannagari , Ezeogo Obaji , Päivi Joensuu , Taina Pihlajaniemi , Lari Lehtiö Chemmedchem DOI: 10.1002/cmdc.201300337 PMID: 24130191 Diamond Proposal Number(s): [8030] Show Abstract ▼ Abstract: Human tankyrases are attractive drug targets, especially for the treatment of cancer. We identified a SET of highly potent tankyrase inhibitors based on a 2-phenyl-3,4-dihydroquinazolin-4-one scaffold. Substitutions at the para position of the scaffold′s phenyl group were evaluated as a strategy to increase potency and improve selectivity. The best compounds displayed single-digit nanomolar potencies, and profiling against several human diphtheria-toxin-like ADP-ribosyltransferases revealed that a subset of these compounds are highly selective tankyrase inhibitors. The compounds also effectively inhibit Wnt signaling in HEK293 cells. The binding mode of all inhibitors was studied by protein X-ray crystallography. This allowed us to establish a structural basis for the development of highly potent and selective tankyrase inhibitors based on the 2-phenyl-3,4-dihydroquinazolin-4-one scaffold and outline a rational approach to the modification of other inhibitor scaffolds that bind to the nicotinamide site of the catalytic domain.	Oct 2013

Instruments / Technical Area

Publication Details

Published

Actions

I04-Macromolecular Crystallography

Para substituted 2-phenyl-3,4-dihydroquinazolin-4-ones as potent and selective tankyrase inhibitors

Teemu Haikarainen , Jarkko Koivunen , Mohit Narwal , Harikanth Venkannagari , Ezeogo Obaji , Päivi Joensuu , Taina Pihlajaniemi , Lari Lehtiö

Chemmedchem

DOI: 10.1002/cmdc.201300337

PMID: 24130191

Diamond Proposal Number(s): [8030]

Show Abstract ▼