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
140
DOIs
出版狀態已發佈 - 十一月 10 2017

指紋

Ubiquitin-Protein Ligases
Multiple Myeloma
Tumors
Lead compounds
Growth
Heterografts
Neoplasms
1,4-naphthoquinone

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

引用此文

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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}",
year = "2017",
month = "11",
day = "10",
doi = "10.1016/j.ejmech.2017.09.011",
language = "English",
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pages = "84--91",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

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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 - 2017/11/10

Y1 - 2017/11/10

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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U2 - 10.1016/j.ejmech.2017.09.011

DO - 10.1016/j.ejmech.2017.09.011

M3 - Article

VL - 140

SP - 84

EP - 91

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

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