Details

Autor(en) / Beteiligte

• Bregman, Howard
• Chakka, Nagasree
• Guzman-Perez, Angel
• Gunaydin, Hakan
• Gu, Yan
• Huang, Xin
• Berry, Virginia
• Liu, Jingzhou
• Teffera, Yohannes
• Huang, Liyue
• Egge, Bryan
• Mullady, Erin L
• Schneider, Steve
• Andrews, Paul S
• Mishra, Ankita
• Newcomb, John
• Serafino, Randy
• Strathdee, Craig A
• Turci, Susan M
• Wilson, Cindy
• DiMauro, Erin F

Titel

Discovery of Novel, Induced-Pocket Binding Oxazolidinones as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors

Ist Teil von

• Journal of medicinal chemistry, 2013-06, Vol.56 (11), p.4320-4342

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates β-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of β-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (39, 40).