Apoptosis signal-regulating kinase 1 (ASK1) has recently emerged as an attractive therapeutic target for the treatment of cardiac and neurodegenerative disorders. The selective inhibitors of ASK1 may become important compounds for the development of clinical agents. We have identified the ASK1 inhibitor among 3H-naphtho[1,2,3-de]quinoline-2,7-diones using receptor-based virtual screening. In vitro kinase assay revealed that ethyl 2,7-dioxo-2,7-dihydro-3H-naphtho[1,2,3-de]quinoline-1-carboxylate (NQDI-1) inhibited ASK1 with a K_i of 500 nM. The competitive character of inhibition is demonstrated in Lineweaver−Burk plots. In our preliminary selectivity study this compound exhibited strong specific inhibitory activity toward ASK1.

中文翻译：

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3 H-萘[1,2,3- de ]喹啉-2,7-二酮类化合物作为凋亡信号调节激酶1（ASK1）抑制剂的鉴定

凋亡信号调节激酶1（ASK1）最近已成为治疗心脏和神经退行性疾病的有吸引力的治疗靶标。ASK1的选择性抑制剂可能成为开发临床药物的重要化合物。我们已经使用基于受体的虚拟筛选在3 H-萘[1,2,3- de ] quinoline-2,7-diones中鉴定了ASK1抑制剂。体外激酶测定表明，2,7-二氧代-2,7-二氢-3 H-萘[1,2,3- de ]喹啉-1-羧酸乙酯（NQDI-1）用K _i抑制ASK1。500 nM。抑制的竞争特征在Lineweaver-Burk图中得到了证明。在我们的初步选择性研究中，该化合物对ASK1表现出很强的特异性抑制活性。