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.

中文翻译：

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高度选择性的坦科聚合酶抑制剂的发现，该抑制剂显示针对多种肿瘤来源细胞系的生长抑制作用

针对特定蛋白质靶标的高质量探针的可用性对于研究其功能及其作为治疗靶标的有效性至关重要。我们报告了利用亲和力富集技术与高分辨率蛋白质质谱相结合的专用化学旋转测定平台，来发现新型烟酰胺等位基因，四唑并喹喔啉41，一种高效且选择性的坦科酶抑制剂。我们还描述了使用41来研究坦科聚合酶的生物学特性，揭示了该化合物诱导了许多肿瘤衍生细胞系的生长抑制，证明了坦科聚合酶抑制剂在肿瘤学中的潜力。