Aberrant activation of the Wnt pathway has been implicated in the development and formation of many cancers. TNKS inhibition has been shown to antagonize Wnt signaling via Axin stabilization in APC mutant colon cancer cell lines. We employed structure-based design to identify a series of 2-aminopyridine oxazolidinones as potent and selective TNKS inhibitors. These compounds exhibited good enzyme and cell potency as well as selectivity over other PARP isoforms. Co-crystal structures of these 2-aminopyridine oxazolidinones complexed to TNKS reveal an induced-pocket binding mode that does not involve interactions with the nicotinamide binding pocket. Oral dosing of lead compounds <b>3</b> and <b>4</b> resulted in significant effects on several...
Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, ther...
Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, ther...
The canonical WNT pathway plays an important role in cancer pathogenesis. Inhibition of poly(ADP-ri...
The Wnt signaling pathway is critical to the regulation of key cellular processes. When deregulated,...
The Wnt signaling pathway is critical to the regulation of key cellular processes. When deregulated,...
The canonical Wnt pathway plays an important role in embryonic development, adult tissue homeostasis...
Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin p...
Tankyrases (TNKSs) have recently gained great consideration as potential targets in Wnt/β-catenin pa...
Tankyrases (TNKSs) are poly(ADP-ribose)polymerases (PARPs) that are overexpressed in several clinic...
Tankyrases (TNKSs) are poly(ADP-ribose)polymerases (PARPs) that are overexpressed in several clini...
Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets ...
Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets ...
More than 80% of colorectal cancer patients have adenomatous polyposis coli (APC) mutations, which i...
Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase (PARP) family. They have...
Abstract Tankyrases (TNKSs) are enzymes specialized in catalyzing poly-ADP-ribosylation of target p...
Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, ther...
Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, ther...
The canonical WNT pathway plays an important role in cancer pathogenesis. Inhibition of poly(ADP-ri...
The Wnt signaling pathway is critical to the regulation of key cellular processes. When deregulated,...
The Wnt signaling pathway is critical to the regulation of key cellular processes. When deregulated,...
The canonical Wnt pathway plays an important role in embryonic development, adult tissue homeostasis...
Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin p...
Tankyrases (TNKSs) have recently gained great consideration as potential targets in Wnt/β-catenin pa...
Tankyrases (TNKSs) are poly(ADP-ribose)polymerases (PARPs) that are overexpressed in several clinic...
Tankyrases (TNKSs) are poly(ADP-ribose)polymerases (PARPs) that are overexpressed in several clini...
Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets ...
Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets ...
More than 80% of colorectal cancer patients have adenomatous polyposis coli (APC) mutations, which i...
Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase (PARP) family. They have...
Abstract Tankyrases (TNKSs) are enzymes specialized in catalyzing poly-ADP-ribosylation of target p...
Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, ther...
Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, ther...
The canonical WNT pathway plays an important role in cancer pathogenesis. Inhibition of poly(ADP-ri...