Cinaciguat
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Cinaciguat(BAY-58-2667)是NO不依赖的sGC激活剂,作用于游离血红素/氧化sGC,EC50值约为10 nM[1]。
血红素相关功能障碍可导致心血管疾病,并伴随可溶性鸟苷酸环化酶(sGC)血红素的氧化,其与这些心血管疾病中的一些相关。sGC是一氧化氮的主要受体,刺激第二信使cGMP的产生,而活性氧可清除NO和氧化/失活血红素,导致sGC降解。Cinaciguat的结合引起α-螺旋旋转,远离血红素口袋,从而抑制His105-血红素之间共价键[2]。
Cinaciguat激活sGC,其EC50和Kd值在低纳摩尔范围,这使得该化合物成为迄今为止所报道的最有效的NO不依赖的sGC激活剂。而且,cinaciguat与NO供体联合使用时会产生一种附加的、非协同效应。Cinaciguat还可以高效地松弛血管,其幅度要比NO供体硝普钠(SNP)和3-morpho-linosydnonimin大几个数量级。此外,cinaciguat在大鼠Langendorff心脏样品中可减少冠状动脉灌注压,而在对硝酸甘油耐受的组织中仍保持活性[1]。
Cinaciguat可以保护心肌细胞免受缺血/再灌注损伤。在兔子中,cinaciguat在I/R前和再灌注时给药可分别减少63%和41%的梗死面积。此外,在小鼠中,cinaciguat预处理可引起更强的80%的梗死面积减少,通过心脏和心肌细胞中cGMP-PKG依赖性H2S的产生,在I/R后可保留心脏功能。而在再灌注时给药仅减少63%的梗死面积[3]。
参考文献:
[1] Evgenov, Oleg V. , et al. "NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential." Nature reviews Drug discovery 5.9 (2006): 755-768.
[2] Martin, Faye, et al. "Structure of cinaciguat (BAY 58–2667) bound to Nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase." Journal of Biological Chemistry 285.29 (2010): 22651-22657.
[3] Salloum, Fadi N. , et al. "Cinaciguat, a novel activator of soluble guanylate cyclase, protects against ischemia/reperfusion injury: role of hydrogen sulfide."American Journal of Physiology-Heart and Circulatory Physiology 302.6 (2012): H1347-H1354.
Storage | Store at -20°C |
M.Wt | 565.7 |
Cas No. | 329773-35-5 |
Formula | C36H39NO5 |
Synonyms | BAY 58-2667 |
Solubility | Soluble in DMSO |
Chemical Name | 4-[[4-carboxybutyl-[2-[2-[[4-(2-phenylethyl)phenyl]methoxy]phenyl]ethyl]amino]methyl]benzoic acid |
SDF | Download SDF |
Canonical SMILES | C1=CC=C(C=C1)CCC2=CC=C(C=C2)COC3=CC=CC=C3CCN(CCCCC(=O)O)CC4=CC=C(C=C4)C(=O)O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
描述 | Cinaciguat (BAY 58-2667)是一种新型的可溶性鸟苷酸环化酶(sGC)激活剂。 | |||||
靶点 | sGC | |||||
IC50 |