1,4-Naphthoquinones as inhibitors of Itch, a HECT domain-E3 ligase, and tumor growth suppressors in multiple myeloma

Yi Min Liu; Wei Chun HuangFu; Han Li Huang; Wei Cheng Wu; Yi Lin Chen; Yun Yen; Hsiang Ling Huang; Chih Ying Nien; Mei Jung Lai; Shiow Lin Pan; Jing Ping Liou

doi:10.1016/j.ejmech.2017.09.011

1,4-Naphthoquinones as inhibitors of Itch, a HECT domain-E3 ligase, and tumor growth suppressors in multiple myeloma

Yi Min Liu, Wei Chun HuangFu, Han Li Huang, Wei Cheng Wu, Yi Lin Chen, Yun Yen, Hsiang Ling Huang, Chih Ying Nien, Mei Jung Lai, Shiow Lin Pan, Jing Ping Liou

研究成果: 雜誌貢獻 › 文章 › 同行評審

17 引文斯高帕斯（Scopus）

摘要

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.

原文	英語
頁（從 - 到）	84-91
頁數	8
期刊	European Journal of Medicinal Chemistry
卷	140
DOIs	https://doi.org/10.1016/j.ejmech.2017.09.011
出版狀態	已發佈 - 2017

ASJC Scopus subject areas

藥理
藥物發現
有機化學

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10.1016/j.ejmech.2017.09.011

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title = "1,4-Naphthoquinones as inhibitors of Itch, a HECT domain-E3 ligase, and tumor growth suppressors in multiple myeloma",

abstract = "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.",

keywords = "HECT domain E3 ligase inhibitor, Naphthoquinone",

author = "Liu, {Yi Min} and HuangFu, {Wei Chun} and Huang, {Han Li} and Wu, {Wei Cheng} and Chen, {Yi Lin} and Yun Yen and Huang, {Hsiang Ling} and Nien, {Chih Ying} and Lai, {Mei Jung} and Pan, {Shiow Lin} and Liou, {Jing Ping}",

note = "Publisher Copyright: {\textcopyright} 2017",

year = "2017",

doi = "10.1016/j.ejmech.2017.09.011",

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journal = "European Journal of Medicinal Chemistry",

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T1 - 1,4-Naphthoquinones as inhibitors of Itch, a HECT domain-E3 ligase, and tumor growth suppressors in multiple myeloma

AU - Liu, Yi Min

AU - HuangFu, Wei Chun

AU - Huang, Han Li

AU - Wu, Wei Cheng

AU - Chen, Yi Lin

AU - Yen, Yun

AU - Huang, Hsiang Ling

AU - Nien, Chih Ying

AU - Lai, Mei Jung

AU - Pan, Shiow Lin

AU - Liou, Jing Ping

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - HECT domain E3 ligase inhibitor

KW - Naphthoquinone

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DO - 10.1016/j.ejmech.2017.09.011

M3 - Article

C2 - 28923389

AN - SCOPUS:85029431769

SN - 0223-5234

VL - 140

SP - 84

EP - 91

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

1,4-Naphthoquinones as inhibitors of Itch, a HECT domain-E3 ligase, and tumor growth suppressors in multiple myeloma

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