5C5R

CRYSTAL STRUCTURE OF HUMAN TANKYRASE-2 IN COMPLEX WITH A PYRANOPYRIDONE INHIBITOR

Summary for 5C5R

• Entry DOI: 10.2210/pdb5c5r/pdb
• Related: 5C5P 5C5R
• Descriptor: Tankyrase-2, ZINC ION, (7R)-2-hydroxy-7-(propan-2-yl)-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonitrile, ... (6 entities in total)
• Functional Keywords: wnt-signalling, beta-catenin, parp-domain, adp-ribosylation, axin, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: Q9H2K2 Q9H2K2
• Total number of polymer chains: 4
• Total formula weight: 55587.10

Authors

Lukacs, C.M.,Janson, C.A. (deposition date: 2015-06-21, release date: 2015-08-12, Last modification date: 2023-09-27)

Primary citation

de Vicente, J.,Tivitmahaisoon, P.,Berry, P.,Bolin, D.R.,Carvajal, D.,He, W.,Huang, K.S.,Janson, C.,Liang, L.,Lukacs, C.,Petersen, A.,Qian, H.,Yi, L.,Zhuang, Y.,Hermann, J.C.
Fragment-Based Drug Design of Novel Pyranopyridones as Cell Active and Orally Bioavailable Tankyrase Inhibitors.
Acs Med.Chem.Lett., 6:1019-1024, 2015

PubMed Abstract: Tankyrase activity has been linked to the regulation of intracellular axin levels, which have been shown to be crucial for the Wnt pathway. Deregulated Wnt signaling is important for the genesis of many diseases including cancer. We describe herein the discovery and development of a new series of tankyrase inhibitors. These pyranopyridones are highly active in various cell-based assays. A fragment/structure based optimization strategy led to a compound with good pharmacokinetic properties that is suitable for in vivo studies and further development.

PubMed: 26396691
DOI: 10.1021/acsmedchemlett.5b00251

Experimental method

X-RAY DIFFRACTION (1.55 Å)