A series of 1,4-naphthoquinones (10a-10q) were synthesized and evaluated for anticancer activity. Compound 10e was identified as an inhibitor of Itch, a HECT domain-E3 ligase. In an evaluation of in vivo efficacy, 10e exhibited remarkable anticancer activity with TGI values of 98.3% and 100% at 25 mg/kg and 50 mg/kg orally daily, respectively, against human RPMI-8226 multiple myeloma xenograft. Treatment with 10e also showed a decrease of Itch level in human RPMI-8226 multiple myeloma cells. Thus 10e is a lead compound for further development of inhibitors targeting E3 ligase for treatment of multiple myeloma.

合成了一系列的1,4-萘醌（10a - 10q）并评估了其抗癌活性。化合物10e被鉴定为Itch的抑制剂，HECT结构域-E3连接酶。在体内功效评估中，10e对人RPMI-8226多发性骨髓瘤异种移植物的抗癌活性表现出显着的抗癌活性，分别每天口服25 mg / kg和50 mg / kg时的TGI值分别为98.3％和100％。用10e进行的治疗还显示人RPMI-8226多发性骨髓瘤细胞中的瘙痒水平降低。因此10e是用于进一步开发靶向E3连接酶的抑制剂以治疗多发性骨髓瘤的先导化合物。