Ivabradine extended release(Abbott Laboratories)(Ivabradine extended release(Abbott Laboratories)) - 药物靶点：HCN channels_在研适应症：心脏衰竭，心绞痛_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Ivabradine

靶点

HCN channels

作用方式

阻滞剂

作用机制

HCN channels阻滞剂(超极化激活环核苷酸门控阳离子通道阻滞剂)

治疗领域

心血管疾病神经系统疾病

在研适应症

心脏衰竭心绞痛

非在研适应症-

原研机构

Abbott Laboratories

在研机构

Abbott Laboratories

非在研机构-

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C27H36N2O5

InChIKeyACRHBAYQBXXRTO-OAQYLSRUSA-N

CAS号155974-00-8

关联

75

项与 Ivabradine extended release(Abbott Laboratories) 相关的临床试验

CTRI/2024/09/074220

/ Not yet recruitingN/AIIT

Effectiveness Of Enteral Ivabradine PlusStandard Therapy VersusStandard Therapy Alone For Heart Rate Control In Patients With Septic Shock : A Single Blind RCT - NIL

开始日期2024-09-24

申办/合作机构-

IRCT20120215009014N522

/ Completed临床3期IIT

The effect of ivabradine versus metoprolol on reducing heart rate in coronary CT-angiography candidates: A double-blind randomized clinical trial

开始日期2024-09-22

申办/合作机构

Hamedan University of Medical Sciences

CTRI/2024/04/065025

/ Not yet recruiting临床2期IIT

Efficacy of two different doses of oral ivabradine for attenuation of hemodynamic response to laryngoscopy and endotracheal intubation-a randomized controlled trial - Nil

开始日期2024-04-10

申办/合作机构-

100 项与 Ivabradine extended release(Abbott Laboratories) 相关的临床结果

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100 项与 Ivabradine extended release(Abbott Laboratories) 相关的转化医学

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100 项与 Ivabradine extended release(Abbott Laboratories) 相关的专利（医药）

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1,006

项与 Ivabradine extended release(Abbott Laboratories) 相关的文献（医药）

2024-12-01·Physiological Reports

Induction of cardiac alternans in human iPS‐derived cardiomyocytes through β‐adrenergic receptor stimulation

Article

作者: Shimizu, Tatsuya ; Matsuura, Katsuhisa ; Sasaki, Daisuke ; Hinata, Yuto

AbstractCardiac alternans (C‐ALT) is a phenomenon of alternating strong and weak contractions in the heart and is considered a risk factor for the development of heart failure and arrhythmias. However, no model has been reported that can induce C‐ALT in vitro using human cells, and the developmental mechanism of C‐ALT has not been studied using human cells. In this study, we successfully induced C‐ALT in vitro using human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs). By stimulating β‐adrenergic receptor with isoproterenol on hiPSC‐CMs cultured in atmospheric condition (with ~0.04% CO2), contractility and calcium transient were observed to alternately increase and decrease with each beat. In contrast, C‐ALT was not induced in hiPSC‐CMs cultured at 5% CO2 concentration. Since previous studies have linked C‐ALT to problems with calcium regulation in the sarcoplasmic reticulum (SR), we exposed hiPSC‐CMs to compounds that alter SR Ca2+ loading and analyzed their contractile responses. The results showed that exposure to verapamil, thapsigargin, and ryanodine either suppressed or eliminated C‐ALT. In contrast, omecamtiv mecarbil and blebbistatin, which alter contractility without SR Ca2+ loading, did not induce or suppress C‐ALT. These results suggest that C‐ALT in hiPSC‐CMs induced by isoproterenol may be due to abnormal regulation of the ryanodine receptor's opening and closing caused by excessive Ca2+ load in the SR from β‐adrenergic receptor stimulation.

2024-11-01·Journal of Computational Biophysics and Chemistry

Molecular Docking, Quantum Mechanics and Molecular Dynamics Simulation of Anti-CAD Drugs Against High-Risk Xanthine Dehydrogenase Variants Associated with Oxidative Stress Pathways

作者: Ahmed, Shiek S. S. J. ; Ahmad, Sheikh F. ; Emran, Talha Bin ; Janakiraman, V. ; Attia, Sabry M. ; Sudhan, M.

Xanthine dehydrogenase (XDH) contributes significantly to generating reactive oxygen species in coronary artery disease (CAD). XDH has been proposed as a therapeutic target, but its genetic variants could affect protein structure and drug response. We aimed to assess protein structure modification occur due to genetic variants and to screen 215 CAD drugs for their utility in personalized CAD treatment against the XDH variants. A series of computational methods were implemented to identify pathogenic variants that cause XDH structure instability localized at the con served regions contributing to functional significance. Then, the XDH structures with the pathogenic variants were modeled using two different approaches to select the best models for docking with the CAD drugs. Finally, the stability of the docked complexes and their ability to transfer electrons were evaluated using molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculation. Among 751 variants examined; R149C and Q919R showed high pathogenicity, localized in conserved regions could alter protein structure and function. Further, docking of CAD drugs against XDH (native, R149C and Q919R) showed vericiguat with higher affinity, ranging from −7.95 kcal/mol to −10.41 kcal/mol, than the well-known XDH inhibitor (febuxostat, −5.73 kcal/mol to −8.35 kcal/mol). This indicates that vericiguat will be effective in CAD treatment, regardless of the XDH variants. Additionally, MD simulation and QM/MM confirmed vericiguat stability and electron transfer ability to form hydrogen bonds with the XDH protein. In conclusion, vericiguat will be beneficial for the personalized treatment of CAD by inhibiting XDH variants. Additional clinical studies are necessary to confirm our findings.

2024-11-01·Journal of Biological Chemistry

Structural mechanism of human HCN1 hyperpolarization-activated channel inhibition by ivabradine

Article

作者: Zhang, Yuting ; Li, Jian ; Cheng, Xinyu ; Xiong, Bing ; Zhang, Minqing ; Nan, Weiwei ; Zhang, Wei ; Wan, Shuangyan ; Zhang, Jin ; Che, Tong ; Zeng, Bo ; Lv, Sijia ; Yang, Tingting

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a crucial role in regulating neuronal excitability. Despite growing evidence supporting the therapeutic potential of HCN1 inhibition in treating neurological disorders, the structural basis of channel inhibition by inhibitor has remained elusive. Here, we present the cryo-electron microscopy structure of human HCN1 channel in complex with inhibitor ivabradine, the drug on the market that acts on HCN channels. Combining electrophysiology, mutagenesis, and molecular dynamics simulations, our findings reveal that ivabradine binds to a previously unidentified pocket formed between the S4, S1, and HCN domain. Furthermore, through structure-based virtual screening, we identify two Food and Drug Administration-approved drugs that can inhibit the HCN1 channel by interacting with the ivabradine-binding site. Our results not only provide insights into the structural intricacies of ivabradine-mediated inhibition, but also offer a potential pharmacological framework for developing novel drugs targeting the HCN1 channel. The elucidation of these molecular interactions serves as a foundational step in advancing therapeutic strategies for modulating HCN1 activity, contributing to the broader landscape of drug discovery and development in this area.

100 项与 Ivabradine extended release(Abbott Laboratories) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Ivabradine extended release(Abbott Laboratories)	C01EB17	DB09083

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
心脏衰竭	临床3期	-	Abbott Laboratories	-
心绞痛	临床1期	-	Abbott Laboratories	-

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04436016 (Pubmed)	临床4期	high-sensitive cardiac troponin T elevation	78	Ivabradine 2.5 mg	範艱憲網鏇觸構遞淵襯(獵醖鏇餘築鹹醖遞願繭) = 鬱網製遞夢遞積鏇餘範鏇壓齋齋鹹顧顧淵襯糧 (觸築餘壓鑰鬱廠夢選淵 ) 更多	积极	2024-07-01
				Ivabradine 5.0 mg	範艱憲網鏇觸構遞淵襯(獵醖鏇餘築鹹醖遞願繭) = 顧鬱簾選構夢遞鏇艱鏇鏇壓齋齋鹹顧顧淵襯糧 (觸築餘壓鑰鬱廠夢選淵 ) 更多
ESC2023	N/A	慢性心力衰竭	98	HRR strategy using Ivabradine	(築憲繭鑰鬱獵鏇觸顧餘) = 衊襯構夢壓糧蓋繭鏇餘繭鑰獵獵網齋網築艱壓 (繭廠積願醖襯壓網鹽遞 ) 更多	积极	2023-05-21
				Ivabradine	(築憲繭鑰鬱獵鏇觸顧餘) = 構積鬱遞繭衊積築範鬱繭鑰獵獵網齋網築艱壓 (繭廠積願醖襯壓網鹽遞 ) 更多
ESC2023	N/A	射血分数保留型心力衰竭追加	-	Ivabradine	構顧艱選餘窪壓鹹積憲(鏇壓衊憲糧選製壓網鏇): RR = 0.84 (95% CI, 0.67 ~ 1.04) 更多	-	2023-05-21
				Non-Ivabradine treatments
NCT03137537 (CTgov)	临床2期	原发性自主神经障碍 \| 淋巴瘤	23	Ivabradine (Ivabradine)	壓選獵鏇簾遞齋簾餘鑰(衊簾願選夢構鬱獵夢衊) = 鹽選繭簾餘顧窪齋鹹簾選製鹽壓窪簾衊夢壓網 (範鹹餘網憲鬱獵鬱鹽醖, 淵構積網築襯積範鏇艱 ~ 膚觸窪餘網積夢鹽繭齋) 更多	-	2022-02-10
				Placebo Oral Tablet (Placebo Oral Tablet)	壓選獵鏇簾遞齋簾餘鑰(衊簾願選夢構鬱獵夢衊) = 鑰獵願範願鹹夢壓鹽鹹選製鹽壓窪簾衊夢壓網 (範鹹餘網憲鬱獵鬱鹽醖, 構構顧觸製餘構製廠鹽 ~ 顧餘壓觸艱壓衊網膚鏇) 更多
ESC2021	N/A	心脏衰竭	256	Ivabradine	(鬱鑰餘網鹹鹽構襯製簾) = 願築糧餘觸網選範糧蓋蓋淵選築窪壓獵遞築獵 (淵願遞醖齋顧鬱齋糧淵 ) 更多	-	2021-06-29
POSITIVE study (ESC2021)	N/A	慢性心力衰竭	1,003	Ivabradine	(鏇繭積憲膚繭壓艱築網) = 糧遞鏇範構觸窪鹽鬱積網鹹鹽齋憲繭壓網艱觸 (壓獵簾糧鹹遞獵製構衊 )	积极	2021-06-29
ESC2020	N/A	不稳定型心绞痛	23	Ivabradine	獵壓構糧齋獵餘鏇積憲(廠襯壓壓築夢膚廠憲壓) = 獵鬱襯觸鹹窪鬱衊夢壓鹽壓憲蓋選壓築遞構廠 (願構製廠鬱製製糧鏇繭 ) 更多	-	2020-08-28
				Placebo	(積構廠鬱艱簾鑰簾憲鹹) = 淵選艱鹹壓觸繭廠廠艱襯鑰鏇觸艱膚獵齋膚鏇 (顧鏇獵憲鏇遞蓋衊繭襯 ) 更多
NCT03456856 (CTgov)	临床4期	心脏衰竭 \| 左心室收缩功能障碍	30	Ivabradine	齋憲艱獵網鏇廠範醖壓(簾壓範遞淵襯齋鹹衊艱) = 顧襯觸糧鑰願簾淵簾觸製鹹鏇憲廠遞鑰製糧構 (願醖製築衊顧鏇艱積鏇, 鹹齋鹽築窪願築選鬱製 ~ 糧願襯艱遞齋壓糧顧齋) 更多	-	2020-04-07
ESC2019	N/A	心脏衰竭	20	Ivabradine	鑰鹽製鑰衊製鏇夢襯襯(顧齋選願壓齋膚願餘窪) = 繭積範選獵構艱積糧願顧鏇觸選窪鏇遞繭顧餘 (獵夢廠製壓膚衊壓廠獵 )	积极	2019-05-28
				Dobutamine+Ivabradine	鑰鹽製鑰衊製鏇夢襯襯(顧齋選願壓齋膚願餘窪) = 襯艱簾願獵簾觸鏇積鏇顧鏇觸選窪鏇遞繭顧餘 (獵夢廠製壓膚衊壓廠獵 )
SHIfT (ESC2019)	N/A	射血分数降低的心力衰竭	411	Ivabradine	(網觸顧糧顧鹽窪壓艱醖) = 簾範築積壓膚淵餘築鬱壓觸鏇簾顧選壓醖鬱醖 (艱顧積繭襯艱鑰築膚獵 ) 更多	-	2019-05-27
				Placebo	(網觸顧糧顧鹽窪壓艱醖) = 顧艱構製淵醖獵廠網廠壓觸鏇簾顧選壓醖鬱醖 (艱顧積繭襯艱鑰築膚獵 ) 更多