更新于：2024-11-21

Ethacrynate Sodium

利尿酸钠

更新于：2024-11-21

概要

概要

基本信息

药物类型

小分子化药

别名

Ethacrynate sodium (USP)、Xarano

+ [2]

靶点

GSTP1

作用机制

GSTP1抑制剂(谷胱甘肽S-转移酶P抑制剂)

治疗领域

心血管疾病遗传病与畸形泌尿生殖系统疾病+ [1]

在研适应症

腹水水肿先天性心脏缺损+ [1]

非在研适应症-

原研机构

Merck & Co., Inc.

在研机构

Bausch Health Americas, Inc.

非在研机构-

最高研发阶段批准上市

首次获批日期

美国 (1967-01-10),

腹水水肿先天性心脏缺损+ [1]

最高研发阶段(中国)-

特殊审评-

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结构

分子式C13H12Cl2O4

InChIKeyAVOLMBLBETYQHX-UHFFFAOYSA-N

CAS号58-54-8

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关联

100 项与利尿酸钠相关的临床结果

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100 项与利尿酸钠相关的转化医学

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100 项与利尿酸钠相关的专利（医药）

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项与利尿酸钠相关的文献（医药）

2020-10-01·Bioorganic & Medicinal Chemistry Letters4区 · 医学

Synthesis and biological evaluation of ethacrynic acid derivatives bearing sulfonamides as potent anti-cancer agents

4区 · 医学

Article

作者: Suzenet, Franck ; El Kazzouli, Saïd ; Bignon, Jérôme ; El Abbouchi, Abdelmoula ; El Brahmi, Nabil ; Hiebel, Marie-Aude ; Guillaumet, Gérald

A series of ethacrynic acid (2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid) (EA, Edecrin) containing sulfonamides linked via three types of linkers namely 1,2-ethylenediamine, piperazine and 4-aminopiperidine was synthesized and subsequently evaluated in vitro against HL60 and HCT116 cancer cell lines. All the EA analogs, excluding 6a and 6c, showed anti-proliferative activity with IC_50s in the micromolar range (less than 4 uM). Three derivatives 6b, 7b and 7e were selected for their interesting dual activity on HL60 cell line in order to be further evaluated against a panel of cancer cell lines (HCT116, A549, MCF7, PC3, U87-MG and SKOV3) as well as on MRC5 as a normal cell line. These compounds displayed IC₅₀ values in nanomolar range against A549, MCF7, PC3 and HCT116 cell lines, deducing the discovery that piperazine or 4-aminopiperidine is the linker's best choice to develop EA analogs with highly potent anti-proliferative activities own up to 24 nM. Besides, in terms of selectivity, those linkers are more suitable offering safety ratios of up to 63.8.

2016-10-01·European Journal of Medicinal Chemistry1区 · 医学

A novel class of ethacrynic acid derivatives as promising drug-like potent generation of anticancer agents with established mechanism of action

1区 · 医学

Article

作者: Anne-Marie Caminade ; Thierry Cresteil ; Saïd El Kazzouli ; Laure Eloy ; Delphine Courilleau ; Joachim Caron ; Mosto M. Bousmina ; Nabil El Brahmi ; Jean-Pierre Majoral ; Serge Mignani

The well-known diuretic Ethacrynic acid (EA, Edecrin), showing low anti-proliferative activities, was chemically modified at different positions. The new EA derivatives have been tested in vitro in anti-proliferative assays on both tumor KB (epidermal carcinoma) and leukemia HL60 (promyelocytic) cells suitable targets for anticancer activity. Reduction of the α-β double bond of EA completely abolished anti-cancer activities, whereas introduction of either 2-(4-substituted phenyl)ethanamine (series A) or 4-(4-substituted phenyl)piperazine (series B) moieties generated compounds showing moderate to strong anti-proliferative activities against human cancer cell lines. Several substitutions on the phenyl of these two moieties are tolerated. The mechanism of action of the EA derivatives prepared in this study is more complex than the inhibition of glutathione S-transferase π ascribed as unique effect to EA and might help to overcome tumor resistances.

2016-06-01·Bioorganic & Medicinal Chemistry Letters4区 · 医学

Potent anti-proliferative actions of a non-diuretic glucosamine derivative of ethacrynic acid

4区 · 医学

Article

作者: Madala, Hanumantha Rao ; Punganuru, Surendra R ; Mostofa, A G M ; Srivenugopal, Kalkunte S ; Basak, Debasish

Ethacrynic acid (EA), a known inhibitor of the neoplastic marker glutathione S-transferase P1 and other GSTs, exerts a weak antiproliferative activity against human cancer cells. The clinical use of EA (Edecrin) as an anticancer drug is limited by its potent loop diuretic activity. In this study, we developed a non-diuretic 2-amino-2-deoxy-d-glucose conjugated EA (EAG) to target tumors cells via the highly expressed glucose transporter 1 (GLUT1). Cell survival assays revealed that EAG had little effect on normal cells, but was cytotoxic 3 to 4.5-fold greater than EA. Mechanistically, the EAG induced selective cell death in cancer cells by inhibiting GSTP1 and generating abundant reactive oxygen species. Furthermore, EAG induced p21(cip1) expression and a G2/M cell cycle block irrespective of the p53 gene status in tumor cells. These data encourage the development of new EA analogs.

100 项与利尿酸钠相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D04079	利尿酸钠	C03CC01	DBSALT001225

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
腹水	美国	Bausch Health Americas, Inc.	1967-01-10
水肿	美国	Bausch Health Americas, Inc.	1967-01-10
先天性心脏缺损	美国	Bausch Health Americas, Inc.	1967-01-10
肾病综合征	美国	Bausch Health Americas, Inc.	1967-01-10