Monastyrskyi Andrii, Bayle Simon, Quereda Victor, Grant Wayne, Cameron Michael, Duckett Derek, Roush William
Department of Chemistry, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, United States.
Department of Molecular Medicine, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, United States.
Bioorg Med Chem Lett. 2018 Feb 1;28(3):400-404. doi: 10.1016/j.bmcl.2017.12.026. Epub 2017 Dec 13.
The development of a new series of apoptosis signal-regulating kinase 1 (ASK1) inhibitors is described. Starting from purine, pyrimidine and quinazoline scaffolds identified by high throughput screening, we used tools of structure-based drug design to develop a series of potent kinase inhibitors, including 2-arylquinazoline derivatives 12 and 23, with submicromolar inhibitory activities against ASK1. Kinetic analysis demonstrated that the 2-arylquinazoline scaffold ASK1 inhibitors described herein are ATP competitive.
本文描述了一系列新型凋亡信号调节激酶1（ASK1）抑制剂的研发情况。从通过高通量筛选确定的嘌呤、嘧啶和喹唑啉骨架出发，我们运用基于结构的药物设计工具，开发了一系列强效激酶抑制剂，包括2-芳基喹唑啉衍生物12和23，它们对ASK1具有亚微摩尔级别的抑制活性。动力学分析表明，本文所述的2-芳基喹唑啉骨架ASK1抑制剂具有ATP竞争性。
