BQ-123(BQ-123) - 药物靶点：ETA_在研适应症：脑水肿_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

ETA

作用机制

ETA拮抗剂(内皮素A受体拮抗剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

University of Glasgow

Western Infirmary

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C31H42N6O7

InChIKeyVYCMAAOURFJIHD-PJNXIOHISA-N

CAS号136553-81-6

序列信息

Sequence Code 15188913

关联

17

项与 BQ-123 相关的临床试验

NCT03679780 / Completed临床1期IIT

The Effect of Endothelin and L-Arginine on Racial Differences in Vasoconstriction

The goal of the study is to examine the possible mechanisms of impaired cutaneous microvascular function through local heating along with administration of vasoconstrictors.

开始日期2018-10-01

申办/合作机构

The University of Texas at Arlington

NCT04907838 / Unknown statusN/AIIT

Insulin Stimulated Vasodilation in Patients With Type 2 Diabetes

This study evaluates the role of endothelin in insulin stimulated vasodilation and glucose uptake. The subjects will complete an hyperinsulinemic euglycemic clamp with and without blockade of the endothelin receptors.

开始日期2018-05-01

申办/合作机构

University of Southern Denmark

[+1]

NCT02987465 / CompletedN/AIIT

An Observational, Open-label Pilot Study to Evaluate the Effect of Standard-of-care Erythropoiesis-stimulating Agents (Darbepoetin Alfa) on Forearm Blood Flow in Nondialysis-dependent Subjects With Anaemia Associated With Chronic Kidney Disease.

In people diagnosed with chronic kidney disease (CKD) anaemia is a common problem and is often treated with EPO (Erythropoietin). One form of EPO used is Darbepoetin (Aranesp®). EPO is safe to use but it has been associated with a rise in blood pressure (BP) in some individuals. The reasons for this are not clear. To try to explain this, this study will look at how EPO affects certain substances in the blood that influence how blood vessels contract and relax. This will be conducted by infusing small amounts of Acetylcholine, BQ123 and Noradrenaline into the arm vessels of volunteers using an established method called Forearm blood flow (plethysmography). Volunteers recruited for this study will include CKD patients undergoing therapy with Darbepoetin as part of their normal NHS care as well as healthy people not on treatment, who will act as controls. This is an observational pilot study of changes in physiology before and after Darbepoetin. It will provide valuable data for a later study comparing Darbepoetin to novel agents which work via different pathways to treat anaemia.

开始日期2017-02-20

申办/合作机构

Cambridge University Hospitals NHS Foundation Trust

[+1]

100 项与 BQ-123 相关的临床结果

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100 项与 BQ-123 相关的转化医学

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100 项与 BQ-123 相关的专利（医药）

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1,709

项与 BQ-123 相关的文献（医药）

2024-08-21·Clinical Science

Endothelin-1 (ET-1) contributes to senescence and phenotypic changes in brain pericytes in diabetes-mimicking conditions

Article

作者: Ergul, Adviye ; Abdul, Yasir ; Jamil, Sarah ; Edgerton-Fulton, Mia

AbstractDiabetes mediates endothelial dysfunction and increases the risk of Alzheimer’s disease and related dementias. Diabetes also dysregulates the ET system. ET-1-mediated constriction of brain microvascular pericytes (BMVPCs) has been shown to contribute to brain hypoperfusion. Cellular senescence, a process that arrests the proliferation of harmful cells and instigates phenotypical changes and proinflammatory responses in endothelial cells that impact their survival and function. Thus, we hypothesized that ET-1 mediates BMVPC senescence and phenotypical changes in diabetes-like conditions. Human BMVPCs were incubated in diabetes-like conditions with or without ET-1 (1 µmol/L) for 3 and 7 days. Hydrogen peroxide (100 µmol/L H2O2) was used as a positive control for senescence and to mimic ischemic conditions. Cells were stained for senescence-associated β-galactosidase or processed for immunoblotting and quantitative real-time PCR analyses. In additional experiments, cells were stimulated with ET-1 in the presence or absence of ETA receptor antagonist BQ-123 (20 μmol/L) or ETB receptor antagonist BQ-788 (20 μmol/L). ET-1 stimulation increased β-galactosidase accumulation which was prevented by BQ-123. ET-1 also increased traditional senescence marker p16 protein and pericyte-specific senescence markers, TGFB1i1, PP1CA, and IGFBP7. Furthermore, ET-1 stimulated contractile protein α-SMA and microglial marker ostepontin in high glucose suggesting a shift toward an ensheathing or microglia-like phenotype. In conclusion, ET-1 triggers senescence, alters ETA and ETB receptors, and causes phenotypical changes in BMVPCs under diabetes-like conditions. These in vitro findings need to be further studied in vivo to establish the role of ETA receptors in the progression of pericyte senescence and phenotypical changes in VCID.

2024-08-01·Naunyn-Schmiedeberg's Archives of Pharmacology

Doxorubicin alters G-protein coupled receptor-mediated vasocontraction in rat coronary arteries

Article

作者: Sandhu, Hardip ; Wheatley, Mark ; Lozahic, Caroline ; Maddock, Helen

Doxorubicin (Doxo)-associated cardio-and vasotoxicity has been recognised as a serious complication of cancer chemotherapy. The purpose of this novel paper was to determine the effect of Doxo on G-protein coupled receptor (GPCR)-mediated vasocontraction located on vascular smooth muscle cells. Rat left anterior descending artery segments were incubated for 24 h with 0.5 µM Doxo. The vasocontractile responses by activation of endothelin receptor type A (ET_A) and type B (ET_B), serotonin receptor 1B (5-HT_1B) and thromboxane A2 prostanoid receptor (TP) were investigated by a sensitive myography using specific agonists, while the specificity of the GPCR agonists was verified by applying selective antagonists (i.e. ET_A and ET_B agonist = 10^- 14-10^- 7.5 M endothelin-1 (ET-1); ET_A antagonist = 10 µM BQ123; ET_B agonists = 10^- 14-10^- 7.5 M sarafotoxin 6c (S6c) and ET-1; ET_B antagonist = 0.1 µM BQ788; 5-HT_1B agonist = 10^- 12-10^- 5.5 M 5-carboxamidotryptamine (5-CT); 5-HT_1B antagonist = 1 µM GR55562; TP agonist = 10^- 12-10^- 6.5 M U46619; TP antagonist = 1 µM Seratrodast). Our results show that 0.5 µM Doxo incubation of LAD segments leads to an increased VSMC vasocontraction through the ET_B, 5-HT_1B and TP GPCRs, with a 2.2-fold increase in ET_B-mediated vasocontraction at 10^- 10.5 M S6c, a 2.0-fold increase in 5-HT_1B-mediated vasocontraction at 10^- 5.5 M 5-CT, and a 1.3-fold increase in TP-mediated vasocontraction at 10^- 6.5 M U46619. Further studies unravelling the involvement of intracellular GPCR signalling pathways will broaden our understanding of the Doxo-induced vasotoxicity, and thus pave the way to mitigate the adverse effects by potential implementation of adjunct therapy options.

2024-07-01·Physiological Reports

The effect of endothelin a receptor inhibition and biological sex on cutaneous microvascular function in non‐Hispanic Black and White young adults

Article

作者: Quyyumi, Arshed A ; Wong, Brett J ; Otis, Jeffrey S ; Hayat, Matthew J ; Turner, Casey G

AbstractThe purpose of this study was to investigate whether endothelin‐A receptor (ETAR) inhibition in non‐Hispanic Black (NHB) and White (NHW) young adults depends on biological sex. We recruited females during low hormone (n = 22) and high hormone (n = 22) phases, and males (n = 22). Participants self‐identified as NHB (n = 33) or NHW (n = 33). Participants were instrumented with two microdialysis fibers: (1) lactated Ringer's (control) and (2) 500 nM BQ‐123 (ETAR antagonist). Local heating was used to elicit cutaneous vasodilation, and an infusion of 20 mM L‐NAME to quantify NO‐dependent vasodilation. At control sites, NO‐dependent vasodilation was lowest in NHB males (46 ± 13 %NO) and NHB females during low hormone phases (47 ± 12 %NO) compared to all NHW groups. Inhibition of ETAR increased NO‐dependent vasodilation in NHB males (66 ± 13 %NO), in both groups of females during low hormone phases (NHW, control: 64 ± 12 %NO, BQ‐123: 85 ± 11 %NO; NHB, BQ‐123: 68 ± 13 %NO), and in NHB females during high hormone phases (control: 61 ± 11 %NO, BQ‐123: 83 ± 9 %NO). There was no effect for ETAR inhibition in NHW males or females during high hormone phases. These data suggest the effect of ETAR inhibition on NO‐dependent vasodilation is influenced by biological sex and racial identity.

100 项与 BQ-123 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	BQ-123	-	DB12054

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
脑水肿	临床2期	-	Pharmazz, Inc.	-
心律失常	临床前	英国	Western Infirmary	-
脑缺血	临床前	美国	-	-
糖尿病并发症	临床前	日本	-	-
心脏衰竭	临床前	英国	University of Glasgow	-
高血压	临床前	日本	-	-
妊娠期高血压	临床前	美国	-	-
外周血管疾病	临床前	日本	-	-
溃疡	临床前	日本	-	-
糖尿病酮症酸中毒	药物发现	美国	Pharmazz, Inc.	2016-09-10

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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


ISC2023	N/A	-	-	Intranasal BQ-123	淵襯繭繭遞鹽廠憲鏇襯(選構構窪簾獵遞顧廠醖) = 壓鑰簾艱廠觸鹽鑰鹹積衊醖鑰鹽鬱膚選鏇鏇齋 (繭廠獵夢鏇顧製衊齋遞 )	-	2023-02-01
NCT02124824 (CTgov)	早期临床1期	胎儿水肿 \| 心脏衰竭	30	BQ-123 (Arm 1: Control)	糧憲築範鏇壓窪獵糧淵(範膚艱網餘積淵夢鏇顧) = 醖選艱構遞選鹹構窪範夢範齋齋壓齋夢觸顧範 (選構獵鏇夢襯鏇鏇壓鑰, 淵範憲觸衊艱醖網鑰蓋 ~ 網鹹夢鹽鏇鹹齋選願選) 更多	-	2021-12-20
				BQ-123 (Arm 2: Heart Failure)	糧憲築範鏇壓窪獵糧淵(範膚艱網餘積淵夢鏇顧) = 膚蓋蓋積獵衊糧襯廠窪夢範齋齋壓齋夢觸顧範 (選構獵鏇夢襯鏇鏇壓鑰, 艱簾淵壓襯遞廠壓鹽鏇 ~ 網觸衊窪壓壓遞繭艱築) 更多
NCT01395329 (NETS, CTgov)	临床4期	高血压 \| 高血压前期	42	FBF response to Sodium Nitroprusside+Nebivolol+ACh+BQ-788+BQ-123 (Nebivolol)	選餘窪網淵夢觸齋構網(遞積積衊衊選壓鬱構願) = 齋範繭膚範簾壓糧齋壓憲餘窪範選獵簾製壓顧 (網範鹹艱淵鏇廠觸醖網, 積築網蓋鹹遞顧網齋糧 ~ 鑰鹹壓鑰製構餘蓋鑰願) 更多	-	2018-12-06
				FBF response to Sodium Nitroprusside+Metoprolol+ACh+BQ-788+BQ-123 (Metoprolol)	選餘窪網淵夢觸齋構網(遞積積衊衊選壓鬱構願) = 齋齋築鹹網願積鹽夢製憲餘窪範選獵簾製壓顧 (網範鹹艱淵鏇廠觸醖網, 夢壓膚窪範齋醖鬱簾衊 ~ 觸襯膚網夢衊廠鹽構簾) 更多
NCT00759408 (CTgov)	临床2期	肺性高血压	38	BQ-123	範壓願艱構夢鬱襯製獵(衊膚顧廠鬱簾壓簾壓顧) = 願觸憲鏇鏇積網餘淵範廠襯鏇艱構淵觸積簾膚 (鹽餘夢範製憲選齋壓獵, 衊願鑰夢遞遞膚鹹選構 ~ 簾夢築鬱衊構憲鹽窪積) 更多	-	2018-10-24
NCT00586820 (BQ-123, CTgov)	临床2期	心肌再灌注损伤 \| 微血管疾病 \| 非ST段抬高型心肌梗死	23	BQ-123 (BQ-123)	築獵壓糧壓鬱醖壓憲獵(遞網醖顧廠廠築廠積鹽) = 獵鑰繭製構遞衊選壓構積齋糧蓋醖鏇鹹餘鹹選 (鏇觸選鏇鑰網糧鑰淵鬱, 積顧艱廠繭淵壓鏇衊鑰 ~ 廠蓋選夢鑰鬱網糧繭範) 更多	-	2014-07-04
				Placebo (Placebo)	築獵壓糧壓鬱醖壓憲獵(遞網醖顧廠廠築廠積鹽) = 艱齋鏇齋襯積鏇夢獵餘積齋糧蓋醖鏇鹹餘鹹選 (鏇觸選鏇鑰網糧鑰淵鬱, 鹹積鹹網選鬱衊膚獵齋 ~ 憲鬱獵壓鹹製鏇築製構) 更多