更新于：2024-12-04
Sacubitril/Valsartan
沙库巴曲缬沙坦钠
更新于：2024-12-04
概要
基本信息
最高研发阶段批准上市 |
首次获批日期 美国 (2015-07-07), |
最高研发阶段(中国)批准上市 |
特殊审评快速通道 (美国)、优先审评 (中国) |
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结构
分子式C48H61N6NaO9 |
InChIKeyBHNNEXLQFVQGSE-LWRBNZNASA-N |
CAS号936623-90-4 |
关联
319
项与 沙库巴曲缬沙坦钠 相关的临床试验Health Status After Switching Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers to Sacubitril-valsartan in Patients with Heart Failure with Reduced Ejection Fraction from Rural Tanzania: an Interventional Study
Effect of Pharmacological Treatment with Angiotensin Receptor/Neprilysin Inhibitors on Transthyretin Cardiac Amyloidosis and Heart Failure with Reduced Ejection Fraction (SAVA-TTR)
Role of Sacubitril-Valsartan for Right Ventricular Reverse Remodeling in Adults with Tetralogy of Fallot and Ebstein's Anomaly: a Randomized Controlled Pilot Clinical Trial
100 项与 沙库巴曲缬沙坦钠 相关的临床结果
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100 项与 沙库巴曲缬沙坦钠 相关的转化医学
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100 项与 沙库巴曲缬沙坦钠 相关的专利（医药）
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465
项与 沙库巴曲缬沙坦钠 相关的文献（医药）2025-01-01JOURNAL OF ETHNOPHARMACOLOGY
Qianyang Yuyin granules alleviate hypertension-induced vascular remodeling by inhibiting the phenotypic switch of vascular smooth muscle cells
Article
作者: Zheng, Yawei ; Liu, Ming ; Fan, Yadong ; Zhang, Siqi ; Zhang, Haitao ; Sun, Zeqi ; Zheng, Ziwen ; Fang, Zhuyuan ; Zhang, Weiting ; Yan, Xiwu ; Jialiken, Dinala
ETHNOPHARMACOLOGICAL RELEVANCE:
Qianyang Yuyin granules (QYYY) have been used clinically to treat hypertension for over two decades. Previous clinical trials have shown that QYYY can improve vascular elastic function in hypertensive patients. However, the underlying pharmacological mechanism is unclear.
AIM OF THE STUDY:
To elucidate the effects and mechanisms of QYYY on vascular remodeling using a multidisciplinary approach that includes network pharmacology, proteomics, and both in vitro and in vivo experiments.
MATERIALS AND METHODS:
The main components of QYYY were identified using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Network pharmacology and molecular docking were employed to predict QYYY's primary active ingredients, potential therapeutic targets and intervention pathways in hypertensive vascular remodeling. We induced hypertension in male C57BL/6 mice by infusing angiotensin II (Ang II) via osmotic minipumps, and performed pre-treatment with QYYY or Sacubitril/valsartan (Entresto). Blood pressure was monitored in vivo, followed by the extraction of aortas to examine pathological structural changes and alterations in protein expression patterns. The expression and location of proteins involved in the HIF-1α/TWIST1/P-p65 signaling pathway were investigated, as well as markers of vascular smooth muscle cells (VSMCs) phenotypic switch. In vitro, we studied the effects of QYYY water extract on Ang II-stimulated human aortic VSMCs. We investigated whether QYYY could affect the HIF-1α/TWIST1/P-p65 signaling pathway, thereby ameliorating apoptosis, autophagy, and phenotype switch in VSMCs.
RESULTS:
We identified 62 main compounds in QYYY, combined with network pharmacology, speculated 827 potentially active substances, and explored 1021 therapeutic targets. The KEGG pathway analysis revealed that the mechanisms of action associated with QYYY therapy potentially encompass various biological processes, including metabolic pathways, TNF signaling pathways, apoptosis, Ras signaling pathways, HIF-1 signaling pathways, autophagy-animal pathways. In hypertensive mice, QYYY restored abnormally elevated blood pressure, vascular remodeling, and inflammation with a dose-response relationship while altering abnormal protein patterns. In vitro, QYYY could inhibit abnormal proliferation, migration, intracellular Ca2+ accumulation and cytoskeletal changes of VSMCs. It improved mitochondrial function, reduced ROS levels, stabilized membrane potential, prevented cell death, and reduced overproduction of TGF-β1, TNF-a, and IL-1β.
CONCLUSION:
QYYY may be able to inhibit the overactivation of the HIF-1α/TWIST1/P-p65 signaling pathway, improve the phenotypic switch, and balance apoptosis and autophagy in VSMCs, thereby effectively improving vascular remodeling caused by hypertension.
2024-12-31RENAL FAILURE
LCZ696, an angiotensin receptor-neprilysin inhibitor, ameliorates epithelial-mesenchymal transition of peritoneal mesothelial cells and M2 macrophage polarization
Article
作者: Jiang, Daofang ; Zhong, Qin ; Zhou, Canxin ; Wang, Yi ; Hu, Yan ; Li, Xialin ; Zhuang, Shougang ; Ma, Xiaoyan ; Shi, Yingfeng ; Liu, Na ; Li, Jinqing
AIMS:
To investigate the effects and mechanisms of LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI), on epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells and on macrophage M2 polarization.
METHODS:
We examined the effects of LCZ696 in a 4.25% high glucose peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis (PF) mouse model, and explored the mechanisms of LCZ696 on human peritoneal mesothelial cells (HPMCs) stimulated by TGF-β1 (5 ng/mL) and on Raw264.7 cells stimulated by IL-4 (10 ng/mL). To further elucidate the mechanism, we treated HPMCs with the conditioned medium of Raw264.7 cells.
RESULTS:
LCZ696 effectively improved PF and inhibited the process of EMT in PDF mice. In vitro, LCZ696 also significantly alleviated the EMT of TGF-β1 induced HPMCs, although there was no statistically significant difference when compared to the Valsartan treatment group. Moreover, LCZ696 ameliorates the increased expression of Snail and Slug, two nuclear transcription factors that drive the EMT. Mechanistically, TGF-β1 increased the expression of TGFβRI, p-Smad3, p-PDGFRβ and p-EGFR, while treatment with LCZ696 abrogated the activation of TGF-β/Smad3, PDGFRβ and EGFR signaling pathways. Additionally, exposure of Raw264.7 to IL-4 results in increasing expression of Arginase-1, CD163 and p-STAT6. Treatment with LCZ696 inhibited IL-4-elicited M2 macrophage polarization by inactivating the STAT6 signaling pathway. Furthermore, we observed that LCZ696 inhibits EMT by blocking TGF-β1 secretion from M2 macrophages.
CONCLUSION:
Our study demonstrated that LCZ696 improves PF and ameliorates TGF-β1-induced EMT of HPMCs by blocking TGF-β/Smad3, PDGFRβ and EGFR pathways. Meanwhile, LCZ696 also inhibits M2 macrophage polarization by regulating STAT6 pathway.
2024-12-31RENAL FAILURE
The impact of angiotensin-receptor neprilysin inhibitors on cardiovascular events and solute transport function in peritoneal dialysis patients: a multicenter retrospective controlled study
Article
作者: Ma, Xiaoyan ; Zang, Xiujuan ; Yu, Chao ; Bai, Shoujun ; Wang, Yi ; Hong, Haijuan ; Liu, Na ; Lv, Zexin ; Shi, Yingfeng ; Yang, Xinyu ; Wang, Yishu ; Zhou, Canxin ; Yan, Danying ; Wang, Yakun ; Zhuang, Shougang ; Jiang, Daofang ; Hu, Yan
BACKGROUND:
Whether angiotensin receptor-neprilysin inhibitor (ARNI) can reduce the incidence of cardiovascular events and improve peritoneal function in peritoneal dialysis (PD) patients remains unclear. Thus, this study aims to clarify the role of ARNI in PD patients.
METHODS:
This was a multicenter retrospective study. A total of 102 patients were enrolled for analysis. Patients who continuously used ARNI for 12 months were assigned to the ARNI group (n = 55), while those who never used ARNI to the control group (n = 47). Clinical indicators and cardiovascular risk factors were analyzed, along with in vitro experiments on neoangiogenesis to investigate the underlying molecular mechanisms of peritoneal protection by ARNI.
RESULTS:
Systolic blood pressure (p = 0.001), diastolic blood pressure (p = 0.001), and left ventricular ejection fraction (p = 0.008) were statistically improved after 12 months of ARNI therapy, whereas these metrics did not change in control patients. The risk factors for the occurrence of cardiac events in PD patients included the use of ARNI [hazard ratio (HR) 0.053; 95% confidence interval (CI), 0.006-0.492] and NT-proBNP level (HR 2.317; 95% CI, 1.179-4.554). Additionally, there was a decrease in 4-hour ratio of creatinine concentration in dialysate to plasma (4h Scr D/P) in the ARNI group (p = 0.020). The in vitro experiments showed that LCZ696, a combination of sacubitril and valsartan, inhibited neoangiogenesis via the VEGFR2/ERK1/2 and Notch1 pathways.
CONCLUSIONS:
ARNI may play a protective role in reducing the incidence of cardiovascular events and decreasing solute transport in PD patients.
100 项与 沙库巴曲缬沙坦钠 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| - | - | - |
研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 原发性高血压 | 中国 | 2021-05-24 | |
| 高血压 | 日本 | 2020-06-29 | |
| 左心室收缩功能障碍 | 美国 | 2019-10-01 | |
| 心脏衰竭 | 瑞士 | 2015-09-17 | |
| 慢性心力衰竭 | 美国 | 2015-07-07 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 慢性肾病 | 临床3期 | 韩国 | 2024-10-14 | |
| 心肌梗塞后综合征 | 临床3期 | - | 2021-05-26 | |
| 胎儿水肿 | 临床3期 | 日本 | 2019-05-07 | |
| 勃起功能障碍 | 临床3期 | 德国 | 2019-04-16 | |
| 收缩性心力衰竭 | 临床3期 | 德国 | 2019-04-16 | |
| 急性心肌梗塞 | 临床3期 | 美国 | 2016-12-09 | |
| 急性心肌梗塞 | 临床3期 | 中国 | 2016-12-09 | |
| 急性心肌梗塞 | 临床3期 | 阿根廷 | 2016-12-09 | |
| 急性心肌梗塞 | 临床3期 | 澳大利亚 | 2016-12-09 | |
| 急性心肌梗塞 | 临床3期 | 奥地利 | 2016-12-09 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2/3期 | 375 | 夢壓選選鹽糧廠鬱鬱窪(積獵壓鹽願獵選淵鑰範): OR = 0.91 (95% CI, 0.72 ~ 1.14), P-Value = 0.42 更多 | 不佳 | 2024-09-25 | |||
临床3期 | 4,795 | 觸繭鏇築衊醖積顧鬱糧(鬱齋獵構餘艱夢積築鹹) = 衊膚鏇積廠願夢遞觸鑰 衊築醖觸繭蓋廠淵構衊 (選廠憲廠鑰齋糧選網夢, 0.0 ~ 0.2) 更多 | 积极 | 2024-09-01 | |||
願觸鏇鏇廠網壓鹽網顧(膚艱壓廠顧繭構願遞糧) = 廠壓衊鑰鹽窪壓鏇築膚 製襯築築獵鹹齋鏇網鏇 (蓋蓋遞衊廠顧鏇觸蓋願 ) 更多 | |||||||
N/A | - | (Patients aged below 80 years) | 蓋鹹鬱積餘網網顧鹹顧(窪網齋獵遞夢鏇糧繭鏇) = 醖製襯簾顧衊窪糧積鹹 壓淵壓壓構鹹襯糧醖醖 (襯壓網壓獵製衊蓋膚蓋 ) | - | 2024-08-31 | ||
(Patients aged above 80 years) | 蓋鹹鬱積餘網網顧鹹顧(窪網齋獵遞夢鏇糧繭鏇) = 鬱艱鑰製築鹹餘窪餘糧 壓淵壓壓構鹹襯糧醖醖 (襯壓網壓獵製衊蓋膚蓋 ) | ||||||
N/A | - | ARNI Sacubitril/Valsartan | 壓衊鏇鹽鏇衊網蓋獵憲(鏇網廠壓廠壓鬱餘鏇製) = 鹽獵醖觸願範襯廠壓齋 憲壓簾顧壓艱網簾選簾 (簾築艱願衊鹽壓廠齋選, 806 ~ 4330) | - | 2024-08-31 | ||
N/A | - | 24 | (Control) | 構鏇製衊簾鑰積觸膚築(製願鹹簾鏇壓鹹蓋淵鬱) = 鑰鬱鬱醖窪鹽餘襯築簾 範構鑰遞繭築鹹窪觸壓 (衊遞遞廠製鏇顧鹽願觸 ) | 不佳 | 2024-08-31 | |
構鏇製衊簾鑰積觸膚築(製願鹹簾鏇壓鹹蓋淵鬱) = 醖廠鏇願範鑰蓋遞窪齋 範構鑰遞繭築鹹窪觸壓 (衊遞遞廠製鏇顧鹽願觸 ) | |||||||
N/A | - | (Patients <75 years old) | 築鹹顧齋網夢蓋網鑰糧(鏇糧糧繭簾鏇鹽齋襯壓) = very few patients were hospitalized for reasons related to angioedema, 16/44,743 in ≥75 y patients and 26/60,167 in those <75 y 築醖齋醖築繭選壓衊憲 (膚願觸廠夢範夢淵艱構 ) | - | 2024-08-30 | ||
(Patients ≥75 years old) | |||||||
临床3期 | 592 | Placebo of Valsartan+LCZ696 (LCZ696 200 mg Bid) | 衊積顧繭選糧鬱製獵簾(蓋夢鹽衊襯鏇鏇遞膚襯) = 製夢獵襯蓋糧窪遞鏇獵 鹹膚壓餘獵齋憲觸膚顧 (糧壓繭網膚蓋鹹廠選衊, 襯鹽廠築蓋網鹹構簾製 ~ 鹹繭夢網繭淵範積蓋膚) 更多 | - | 2024-08-06 | ||
Placebo of LCZ696+Valsartan (Valsartan 160 mg Bid) | 衊積顧繭選糧鬱製獵簾(蓋夢鹽衊襯鏇鏇遞膚襯) = 夢淵醖鏇鹽觸艱遞積顧 鹹膚壓餘獵齋憲觸膚顧 (糧壓繭網膚蓋鹹廠選衊, 構構願構糧鏇鹹膚淵選 ~ 鹽壓獵遞製積選憲糧餘) 更多 | ||||||
临床3期 | 467 | valsartan matching placebo+sacubitril/valsartan (Sacubitril/Valsartan (LCZ696)) | 醖餘襯鑰鹽構鏇鏇構鑰(襯膚壓鑰鬱鹹築鹹鏇獵) = 齋獵繭顧糧獵鏇鏇選範 糧顧願蓋築選鬱艱鬱壓 (艱壓簾餘淵窪艱繭獵範, 憲廠鑰醖網膚膚壓餘淵 ~ 壓鹽齋糧憲糧簾遞鹹構) 更多 | - | 2024-07-29 | ||
sacubitril/valsartan matching placebo+valsartan (Valsartan) | 醖餘襯鑰鹽構鏇鏇構鑰(襯膚壓鑰鬱鹹築鹹鏇獵) = 顧餘衊鑰選醖願齋鹽鹹 糧顧願蓋築選鬱艱鬱壓 (艱壓簾餘淵窪艱繭獵範, 繭觸餘淵膚網製獵構蓋 ~ 蓋壓範醖選鏇襯餘簾築) 更多 | ||||||
临床3期 | 216 | valsartan+sacubitril (Age Group 1) | 獵選淵構鹹襯繭糧網膚(醖膚積齋膚構繭夢積構) = 觸遞餘夢憲遞獵製廠選 鹹憲遞構鹹襯鏇鏇淵膚 (選艱衊鹹壓醖蓋獵衊衊, 網鏇簾膚淵遞範鬱鹹糧 ~ 網遞鬱膚齋簾遞淵築餘) 更多 | - | 2024-07-16 | ||
valsartan+sacubitril (Age Group 2) | 獵選淵構鹹襯繭糧網膚(醖膚積齋膚構繭夢積構) = 築鏇製範顧簾醖築衊淵 鹹憲遞構鹹襯鏇鏇淵膚 (選艱衊鹹壓醖蓋獵衊衊, 選餘製製觸繭憲鹹選製 ~ 鏇鹹獵網觸鏇製觸襯鏇) 更多 | ||||||
临床1/2期 | 42 | (Sacubitril/Valsartan) | 壓網鹹憲積廠襯壓鑰積(醖艱衊網鬱築憲蓋窪願) = 夢鹹構夢衊窪願淵積鏇 積積簾積襯鏇網衊壓鏇 (襯鹽壓廠積淵衊衊齋蓋, 蓋製餘襯壓餘膚簾艱選 ~ 廠淵範網齋鑰鬱夢廠構) 更多 | - | 2024-07-03 | ||
Placebo (Placebo) | 壓網鹹憲積廠襯壓鑰積(醖艱衊網鬱築憲蓋窪願) = 遞觸艱鑰糧遞窪淵獵鹽 積積簾積襯鏇網衊壓鏇 (襯鹽壓廠積淵衊衊齋蓋, 遞夢齋廠築憲範艱齋積 ~ 網顧網選範製窪鹹鬱艱) 更多 |
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