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

19 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

UN SDG

此研究成果有助於以下永續發展目標

SDG 3 良好的健康和福祉

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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@article{df9ed5767964403aa88a762581320b0f,

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",

language = "English",

volume = "140",

pages = "84--91",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

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TY - JOUR

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

UR - https://www.scopus.com/pages/publications/85029431769

UR - https://www.scopus.com/pages/publications/85029431769#tab=citedBy

U2 - 10.1016/j.ejmech.2017.09.011

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

摘要

UN SDG

ASJC Scopus subject areas

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引用此