1,4-萘醌作为瘙痒（一种HECT结构域E3连接酶）的抑制剂以及多发性骨髓瘤中的肿瘤生长抑制因子。
1,4-Naphthoquinones as inhibitors of Itch, a HECT domain-E3 ligase, and tumor growth suppressors in multiple myeloma.
作者信息
Liu Yi-Min, HuangFu Wei-Chun, Huang Han-Li, Wu Wei-Cheng, Chen Yi-Lin, Yen Yun, Huang Hsiang-Ling, Nien Chih-Ying, Lai Mei-Jung, Pan Shiow-Lin, Liou Jing-Ping
机构信息
School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
出版信息
Eur J Med Chem. 2017 Nov 10;140:84-91. doi: 10.1016/j.ejmech.2017.09.011. Epub 2017 Sep 6.
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1,4-萘醌（10a - 10q）并评估其抗癌活性。化合物10e被鉴定为ITCH（一种HECT结构域E3连接酶）的抑制剂。在体内疗效评估中，10e对人RPMI - 8226多发性骨髓瘤异种移植瘤分别以25mg/kg和50mg/kg的口服剂量每日给药时，表现出显著的抗癌活性，TGI值分别为98.3%和100%。用10e处理还显示人RPMI - 8226多发性骨髓瘤细胞中ITCH水平降低。因此，10e是用于进一步开发靶向E3连接酶抑制剂以治疗多发性骨髓瘤的先导化合物。
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