更新于：2024-09-19

Ouabain

毒毛花苷G

更新于：2024-09-19

概要

概要

基本信息

药物类型

小分子化药

别名

3-(α-L-rhamnopyranosyloxy)-1β,5β,11α,14,19-pentahydroxy-5β-card-20(22)-enolide、G-Strophanthin、G-Strophanthin (JAN)

+ [6]

靶点

ATP1A1

作用机制

钠钾转运ATP酶α1链抑制剂

治疗领域

心血管疾病

在研适应症

心脏衰竭

非在研适应症-

原研机构-

在研机构-

非在研机构-

最高研发阶段批准上市

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C29H60O20

InChIKeyTYBARJRCFHUHSN-DMJRSANLSA-N

CAS号11018-89-6

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关联

100 项与毒毛花苷G 相关的临床结果

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100 项与毒毛花苷G 相关的转化医学

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100 项与毒毛花苷G 相关的专利（医药）

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12,657

项与毒毛花苷G 相关的文献（医药）

2024-10-01·Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Function and regulation of the insect NaCCC2 sodium transport proteins

Article

作者: Gillen, Christopher M ; Piermarini, Peter M ; Romero, Michael F ; Yarcusko, Ryan S ; Song, Maria Hemmi ; Neuger, Grace C

NaCCC2 transport proteins, including those from Drosophila melanogaster (Ncc83) and Aedes aegypti (aeCCC2), are an insect-specific clade with sequence similarity to Na⁺-K⁺-2Cl^- cotransporters. Whereas the Na⁺-K⁺-2Cl^- cotransporters and other cation-chloride cotransporters are electroneutral, recent work indicates that Ncc83 and aeCCC2 carry charge across membranes. Here, we further characterize the regulation and transport properties of Ncc83 and aeCCC2 expressed in Xenopus oocytes. In cation uptake experiments, Li⁺ was used as a tracer for Na⁺ and Rb⁺ was used as a tracer for K⁺. Li⁺ uptake of oocytes expressing either aeCCC2 or Ncc83 was greater than uptake in water-injected controls, activated by hypotonic swelling, and not inhibited by ouabain or ethyl cinnamate. Rb⁺ uptake of oocytes expressing either aeCCC2 or Ncc83 was not different than water injected controls. In oocytes expressing either aeCCC2 or Ncc83, Li⁺ uptake plateaued with increasing Li⁺ concentrations, with apparent K_m values in the range of 10 to 20 mM. Following exposure to ouabain, intracellular [Na⁺] was greater in oocytes expressing aeCCC2 than in controls. Elevating intracellular cAMP (via 8-bromo-cAMP) in Ncc83 oocytes significantly stimulated both Li⁺ uptake and membrane conductances. Elevating intracellular cAMP in aeCCC2 oocytes did not affect Li⁺ uptake, but stimulated membrane conductances. Overall, these results confirm that the NaCCC2s resemble other cation-chloride cotransporters in their regulation and some transport properties. However, unlike other cation-chloride cotransporters, they carry charge across membranes.

2024-09-01·Archives of Biochemistry and Biophysics

Evaluation of the activity of cardiac glycosides on RORγ and RORγT nuclear receptors

Article

作者: Sałkowska, Anna ; Ratajewski, Marcin ; Pastwińska, Joanna ; Karwaciak, Iwona ; Bachorz, Rafał A

Cardiac glycosides, derived from plants and animals, have been recognized since ancient times. These substances hinder the function of the sodium-potassium pump within eukaryotic cells. Many reports have shown that these compounds influence the activity of nuclear receptors. Thus, we assessed the effects of various cardiac glycosides at nontoxic concentrations on RORγ and RORγT. RORγT is a crucial protein involved in the differentiation of Th17 lymphocytes. Sixteen analyzed cardiac glycosides exhibited varying toxicities in HepG2 cells, all of which demonstrated agonistic effects on RORγ, as confirmed in the RORγ-HepG2 reporter cell line. The overexpression of both the RORγ and RORγT isoforms intensified the effects of these compounds. Additionally, these glycosides induced the expression of G6PC, a gene regulated by RORγ, in HepG2 cells. Subsequently, the effects of two endogenous cardiac glycosides (marinobufagenin and ouabain) and the three most potent glycosides (bufalin, oleandrin, and telecinobufagenin) were evaluated in Th17 primary lymphocytes. All of these compounds increased the expression of the IL17A, IL17F, IFNG, and CXCL10 genes, but they exhibited varying effects on GZMB and CCL20 expression. Molecular docking analysis revealed the robust binding affinity of cardiac glycosides for the ligand binding domain of the RORγ/RORγT receptors. Thus, we demonstrated that at nontoxic concentrations, cardiac glycosides have agonistic effects on RORγ/RORγT nuclear receptors, augmenting their activity. This potential can be harnessed to modulate the phenotype of IL17-expressing cells (e.g., Th17 or Tc17 lymphocytes) in adoptive therapy for combating various types of cancer.

2024-08-01·International Journal for Parasitology: Drugs and Drug Resistance

Ouabain, ATPase inhibitor, potentially enhances the effect of polyhexamethylene biguanide on Acanthamoeba castellanii

Article

作者: Shih, Kuang-Yi ; Chang, Yao-Tsung ; Huang, Jian-Ming ; Wang, Yu-Jen

Acanthamoeba, a free-living amoeba, is commonly found in various natural environments, such as rivers and soil, as well as in public baths, swimming pools, and sewers. Acanthamoeba can cause severe illness such as granulomatous amoebic encephalitis and Acanthamoeba keratitis (AK) in humans. AK, the most recognized disease, can cause permanent visual impairment or blindness by affecting the cornea. AK commonly affects contact lens wearers who neglect proper cleaning habits. The symptoms of AK include epithelial and stromal destruction, corneal infiltrate, and intense ocular pain, occasionally necessitating surgical removal of the entire eyeball. Current AK treatment involves the hourly application of eye drops containing polyhexamethylene biocide (PHMB). However, studies have revealed their ineffectiveness against drug-resistant strains. Acanthamoeba can form cysts as a survival mechanism in adverse environments, though the exact mechanism remains unknown. Our experiments revealed that sodium P-type ATPase (ACA1_065450) is closely linked to encystation. In addition, various encystation buffers, such as MgCl₂ or NaCl, induced the expression of P-type ATPase. Furthermore, we used ouabain, an ATPase inhibitor, to inhibit the Na⁺/K⁺ ion pump, consequently decreasing the encystation rate of Acanthamoeba. Our primary objective is to develop an advanced treatment for AK. We anticipate that the combination of ouabain and PHMB may serve as an effective therapeutic approach against AK in the future.

100 项与毒毛花苷G 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00112	毒毛花苷G	C01AC01	DB01092

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
心脏衰竭	-	-	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ERA2023	N/A	急性肾损伤 \| 脓毒症	177	ENDOGENOUS OUABAIN (Patients diagnosed with sepsis or septic shock)	夢鏇網蓋範醖糧衊簾壓(鹽願鹽構繭顧艱製鬱夢) = 網鏇遞鏇築製憲鏇範範繭窪製廠簾夢網築餘獵 (餘鑰襯憲鑰齋膚廠廠繭 ) 更多	-	2023-06-15
ASN2018	N/A	肾细胞癌	-	Ouabain	齋顧鹽繭願網夢獵鬱繭(網窪壓蓋遞膚鹹廠廠觸) = 糧範積襯糧壓艱築憲鬱獵積窪鹽觸窪鏇網鹽淵 (淵膚觸壓獵鬱醖淵醖蓋 )	-	2018-10-23
ASN2016	N/A	糖尿病肾病	-	Ouabain	襯鬱網糧憲窪鹽鹹醖窪(積窪鏇鹽膚餘鹽顧膚鬱) = 遞夢衊願鹽願窪衊廠選衊襯鏇糧蓋壓膚艱積獵 (憲構憲製齋範鏇簾願願, 4.1)	积极	2016-11-15
				Ouabain 5nM	襯鬱網糧憲窪鹽鹹醖窪(積窪鏇鹽膚餘鹽顧膚鬱) = 願觸鹹網鬱顧構網積醖衊襯鏇糧蓋壓膚艱積獵 (憲構憲製齋範鏇簾願願, 1.3)
ASN2014	N/A	蛋白尿 ouabain	-	Rostafuroxin 100 µg/kg/day	(齋淵鏇鏇顧窪範鏇遞醖) = 獵願範窪遞夢齋鏇夢構觸簾網製範鏇齋壓窪築 (願積積築鬱衊範艱簾餘 ) 更多	积极	2014-11-11
				Ouabain	(齋淵鏇鏇顧窪範鏇遞醖) = 鏇鹹醖鬱遞糧製鹽憲艱觸簾網製範鏇齋壓窪築 (願積積築鬱衊範艱簾餘 ) 更多
ASN2014	N/A	高血压 serum uric acid \| endogenous ouabain \| ATP-binding cassette B1 gene	222	Ouabain	糧襯鏇鬱鏇艱蓋鬱憲鬱(築鏇遞廠鑰願簾淵願衊) = 鬱鹽觸憲顧糧餘憲鬱壓鬱鬱積遞鑰願繭糧網築 (齋獵獵網艱鹽觸齋窪遞 )	-	2014-11-11
ASN2012	N/A	志贺氏菌感染 Stx2 \| Gb3 receptors \| Bax ... 更多	-	Ouabain/Na,K-ATPase	蓋艱鑰願簾繭齋餘蓋窪(襯顧膚遞膚醖廠鹹繭蓋) = 製蓋範鏇窪獵蓋鏇鬱築選齋範艱鏇範糧鬱獵鹹 (醖鑰顧願淵願觸襯獵網 ) 更多	积极	2012-10-30
				Ouabain	蓋艱鑰願簾繭齋餘蓋窪(襯顧膚遞膚醖廠鹹繭蓋) = 鏇窪構願艱壓鹽遞艱築選齋範艱鏇範糧鬱獵鹹 (醖鑰顧願淵願觸襯獵網 ) 更多
ASN2010	N/A	高血压 Na-K ATPase \| NHE-1	-	Ouabain	(獵顧糧鬱襯遞簾憲醖構) = 鬱糧壓築廠網範範鬱餘繭衊夢範衊範窪顧繭衊 (遞膚網襯膚鹽壓齋網壓, 3.26)	积极	2010-11-16
				Vehicle	(獵顧糧鬱襯遞簾憲醖構) = 願蓋齋鑰淵遞醖網襯選繭衊夢範衊範窪顧繭衊 (遞膚網襯膚鹽壓齋網壓, 5.32)
ARVO2008	N/A	-	-	Ouabain 30 nM	膚窪觸膚鹽顧繭遞蓋夢(齋齋鏇遞願築積鏇簾糧) = 鹽製簾構構簾餘窪夢醖艱憲顧製獵製願顧願醖 (鏇襯窪範鹹糧壓鹽憲鹹 )	-	2008-05-01
				Ouabain	膚窪觸膚鹽顧繭遞蓋夢(齋齋鏇遞願築積鏇簾糧) = 窪醖顧蓋醖淵遞淵製憲艱憲顧製獵製願顧願醖 (鏇襯窪範鹹糧壓鹽憲鹹 )
ARVO2005	N/A	虹膜色素上皮异常	-	Ouabain	艱鹽蓋憲製齋醖壓齋簾(構願觸襯窪鹽繭廠鬱獵) = ouabain did enhance BKCa-channel activity without a change in single-channel amplitude 鹹壓繭獵壓艱襯淵醖觸 (蓋鹹築衊糧衊簾繭繭膚 )	-	2005-05-01