1. Discovery of a Highly Selective Tankyrase Inhibitor Displaying Growth Inhibition Effects against a Diverse Range of Tumor Derived Cell Lines.
- Author
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Thomson DW, Wagner AJ, Bantscheff M, Benson RE, Dittus L, Duempelfeld B, Drewes G, Krause J, Moore JT, Mueller K, Poeckel D, Rau C, Salzer E, Shewchuk L, Hopf C, Emery JG, and Muelbaier M
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Line, Tumor, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Humans, Ligands, Models, Molecular, Molecular Structure, Quinoxalines chemical synthesis, Quinoxalines chemistry, Structure-Activity Relationship, Tankyrases metabolism, Antineoplastic Agents pharmacology, Drug Discovery, Enzyme Inhibitors pharmacology, Quinoxalines pharmacology, Tankyrases antagonists & inhibitors
- Abstract
The availability of high quality probes for specific protein targets is fundamental to the investigation of their function and their validation as therapeutic targets. We report the utilization of a dedicated chemoproteomic assay platform combining affinity enrichment technology with high-resolution protein mass spectrometry to the discovery of a novel nicotinamide isoster, the tetrazoloquinoxaline 41, a highly potent and selective tankyrase inhibitor. We also describe the use of 41 to investigate the biology of tankyrase, revealing the compound induced growth inhibition of a number of tumor derived cell lines, demonstrating the potential of tankyrase inhibitors in oncology.
- Published
- 2017
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