TITLE: lndolinyl-Sulfonamide Inhibitors of Tankyrase
INVENTORS: Lawrence Lum
TECHNOLOGY: Biologicals
UTSD: 2934
SUMMARY: IWR-8 is a small molecule identified from a synthetic chemical library screen for novel Wnt pathway inhibitors that target both vertebrate tankyrase (Tnks) enzymes. The Tnks enzymes establish threshold responses to extracellular signals provided by the Wnt family of cell fate determination molecules. Given the prevalence of B-catenin mis-activation in colorectal cancer, IWR-8 represents a potentially useful approach to treatment of this disease.
The PARP superfamily of enzymes, of which Tnks is a member, are promising anti-cancer targets. Selective targeting of PARPS, mostly in the context of cancer, has been a challenge because the most druggable pocket of these enzymes is well-conserved across all 17 family members. IWR-8 uniquely targets the groove that engages the adenosine portion of PARP substrates (NADPH) and induces a small molecule pocket. IWR-8 may be useful to treat diseases associated with increased activation of the Wnt pathway and/or abnormal telomeric extension.
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Phone: 214-648-1888
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Please reference UT Southwestern Case Number: 2934