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

作用方式

拮抗剂

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

权益机构-

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-

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结构/序列

分子式C31H42N6O7

InChIKeyVYCMAAOURFJIHD-PJNXIOHISA-N

CAS号136553-81-6

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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1,965

项与 BQ-123 相关的文献（医药）

2025-05-01·Journal of Applied Physiology

Elevated circulating endothelial cell-derived microvesicles: a biomarker of endothelial vasomotor dysfunction in adults with obesity

Article

作者: Dow, Caitlin A. ; Berry, Auburn R. ; Fandl, Hannah K. ; Garcia, Vinicius P. ; Greiner, Jared J. ; DeSouza, Christopher A. ; Wegerson, Kendra N. ; Stockelman, Kelly A. ; Stauffer, Brian L. ; Park, Andrew J. ; Ruzzene, Samuel T.

Circulating endothelial microvesicles (EMVs) may serve as a key biomarker and mediator of vascular dysfunction in obesity. This study demonstrates that EMV levels are markedly higher in adults with obesity compared with adults with normal weight. Elevated EMVs were associated with impaired endothelial vasodilation and heightened endothelin-1-mediated vasoconstriction. These findings highlight a potential mechanistic link between obesity and cardiovascular disease risk, emphasizing the role of EMVs in vascular health.

2025-03-01·Redox Biology

Endogenous hydrogen sulfide persulfidates endothelin type A receptor to inhibit pulmonary arterial smooth muscle cell proliferation

Article

作者: Liu, Xin ; Tang, Chaoshu ; Geng, Bin ; Huang, Yaqian ; Zhang, Yanan ; Tang, Xinjing ; Zhou, Dan ; Jin, Hongfang ; Tian, Xiaoyu ; Du, Junbao ; Chen, Liangyi ; Zhao, Shiqun

BACKGROUNDThe binding of endothelin-1 (ET-1) to endothelin type A receptor (ETAR) performs a critical action in pulmonary arterial smooth muscle cell (PASMC) proliferation leading to pulmonary vascular structural remodeling. More evidence showed that cystathionine γ-lyase (CSE)-catalyzed endogenous hydrogen sulfide (H₂S) was involved in the pathogenesis of cardiovascular diseases. In this study, we aimed to explore the effect of endogenous H₂S/CSE pathway on the ET-1/ETAR binding and its underlying mechanisms in the cellular and animal models of PASMC proliferation.METHODS AND RESULTSBoth live cell imaging and ligand-receptor assays revealed that H₂S donor, NaHS, inhibited the binding of ET-1/ETAR in human PASMCs (HPASMCs) and HEK-293A cells, along with an inhibition of ET-1-activated HPASMC proliferation. While, an upregulated Ki-67 expression by the pulmonary arteries, a marked pulmonary artery structural remodeling, and an increased pulmonary artery pressure were observed in CSE knockout (CSE-KO) mice with a deficient H₂S/CSE pathway compared with those in the wild type (WT) mice. Meanwhile, NaHS rescued the enhanced binding of ET-1 with ETAR and cell proliferation in the CSE-knockdowned HPASMCs. Moreover, the ETAR antagonist BQ123 blocked the enhanced proliferation of CSE-knockdowned HPASMCs. Mechanistically, ETAR persulfidation was reduced in the lung tissues of CSE-KO mice compared to that in WT mice, which could be reversed by NaHS treatment. Similarly, NaHS persulfidated ETAR in HPASMCs and HEK-293A cells. Whereas a thiol reductant dithiothreitol (DTT) reversed the H₂S-induced ETAR persulfidation and further blocked the H₂S-inhibited binding of ET-1/ETAR and HPASMC proliferation. Furthermore, the mutation of ETAR at cysteine (Cys) 69 abolished the persulfidation of ETAR by H₂S, and subsequently blocked the H₂S-suppressed ET-1/ETAR binding and HPASMC proliferation.CONCLUSIONEndogenous H₂S persulfidated ETAR at Cys69 to inhibit the binding of ET-1 to ETAR, subsequently suppressed PASMC proliferation, and antagonized pulmonary vascular structural remodeling.

2024-12-31·Blood Pressure

Endothelin-1- and acetylcholine-mediated effects in human and rat vessels: impact of perivascular adipose tissue, diabetes, angiotensin II, and chemerin

Article

作者: Danser, A. H. Jan ; Tan, Lunbo ; Cruz-López, Edwyn O. ; Verdonk, Koen ; Stolk, Daniël G. ; van den Bogaerdt, Antoon J.

OBJECTIVETo study the role of perivascular adipose tissue (PVAT) in the reactivity of rat and human vessels.METHODSIliac and mesenteric arteries were obtained from normotensive Sprague-Dawley rats, hypertensive transgenic (mRen2)27 rats overexpressing mouse renin, and (mRen2)27 rats made diabetic with streptozotocin. Human coronary arteries were obtained from donors. Concentration-response curves were constructed to endothelin-1 and acetylcholine with and without PVAT. The contribution of NO and endothelium-dependent hyperpolarization (EDH) were determined making use of the NO synthase inhibitor L-NAME and the EDH inhibitors apamin + TRAM-34. The endothelin type A and type B (ET_A, ET_B) receptor blockers BQ123 and BQ788, the chemerin inhibitors α-NETA and pravastatin, and the angiotensin receptor blocker losartan were also used.RESULTSIn rat iliac arteries, PVAT diminished endothelin-induced constriction, while the opposite was true in human coronaries. Coronary effects were unaltered by α-NETA, pravastatin, or losartan. ET_B receptor-mediated relaxation in iliac arteries occurred only with PVAT, and BQ123 blocked endothelin-1-induced constriction. Diabetes upregulated the anticontractile effects of PVAT. In rat mesenteric arteries, acetylcholine-induced relaxation with PVAT relied on NO, and on NO + EDH without PVAT. Diabetes upregulated the EDH component exclusively with PVAT.CONCLUSIONPVAT modulates ET-1-induced constriction in a vessel type-dependent manner. Its enhancing effects in coronaries involved neither chemerin nor angiotensin II. Its anticontractile effects in rat iliac arteries involved ET_B receptor-mediated relaxation. Diabetes upregulated PVAT's anticontractile effects. In mesenteric arteries, PVAT counterbalanced the EDH component of the relaxant effect of acetylcholine. Diabetes reversed this effect by upregulating the EDH component.

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	-	-
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	-	-
疼痛	药物发现	美国	Pharmazz, Inc.	2017-10-18
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	diabetes	-	Intranasal BQ-123	廠築鑰淵簾簾衊獵鬱襯(鬱蓋網壓範蓋膚築壓選) = 鏇網鏇願築窪餘繭築膚鬱衊簾餘艱醖淵淵衊選 (範齋窪廠膚齋選鹽憲選 )	-	2023-02-01
NCT02124824 (CTgov)	早期临床1期	心脏衰竭	30	BQ-123 (Arm 1: Control)	鏇醖淵膚繭鏇廠壓壓膚(獵獵積遞網繭觸艱衊繭) = 簾觸廠膚積獵襯夢鬱蓋製簾衊簾糧廠製範網艱 (夢繭餘觸糧糧觸憲範衊, 壓鹽遞艱網鹽齋網糧遞 ~ 製齋築糧餘齋齋壓壓艱) 更多	-	2021-12-20
				BQ-123 (Arm 2: Heart Failure)	鏇醖淵膚繭鏇廠壓壓膚(獵獵積遞網繭觸艱衊繭) = 蓋廠夢構鑰醖淵廠窪製製簾衊簾糧廠製範網艱 (夢繭餘觸糧糧觸憲範衊, 鑰遞淵廠艱襯遞構艱糧 ~ 範範鑰鬱繭廠獵製窪齋) 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)	鏇鏇遞鑰壓製襯壓願獵(鏇顧膚糧鹹鹽獵蓋淵夢) = 醖遞蓋淵觸願膚衊淵餘醖鹹願構構糧願淵齋範 (淵網廠鑰憲繭鑰網襯艱, 願觸膚襯膚窪願鏇觸餘 ~ 選夢積憲糧鬱艱壓衊願) 更多	-	2018-12-06
				FBF response to Sodium Nitroprusside+Metoprolol+ACh+BQ-788+BQ-123 (Metoprolol)	鏇鏇遞鑰壓製襯壓願獵(鏇顧膚糧鹹鹽獵蓋淵夢) = 壓壓積艱簾衊獵艱蓋繭醖鹹願構構糧願淵齋範 (淵網廠鑰憲繭鑰網襯艱, 網鏇選積廠蓋壓範構願 ~ 積鹽窪廠膚窪願構鹹夢) 更多
NCT00759408 (CTgov)	临床2期	肺性高血压	38	BQ-123	範鹹觸鬱醖獵醖窪壓艱(襯構顧鏇獵襯壓選壓鏇) = 廠構淵夢衊構糧獵夢夢壓觸願遞積膚選鹽製廠 (遞齋鑰簾願齋鹽夢餘鹽, 選獵膚醖構淵製衊選夢 ~ 衊築衊憲遞網繭鬱構餘) 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)	膚範繭餘鹽觸顧獵襯選(夢襯鹽醖糧簾夢壓鏇構) = 範選膚鏇鏇鑰餘製顧簾鬱選襯簾憲顧鬱願鑰夢 (築鬱積觸醖獵齋鹽淵願, 築餘糧構壓構築糧壓膚 ~ 鹹鹽鏇簾願遞獵壓壓網) 更多	-	2014-07-04
				Placebo (Placebo)	膚範繭餘鹽觸顧獵襯選(夢襯鹽醖糧簾夢壓鏇構) = 襯壓築夢願齋憲繭積鏇鬱選襯簾憲顧鬱願鑰夢 (築鬱積觸醖獵齋鹽淵願, 鏇鑰顧製夢鬱鬱觸蓋獵 ~ 鏇鑰淵鑰糧簾糧鹽廠鹽) 更多