Cinaciguat hydrochloride
(Synonyms: BAY 58-2667 hydrochloride) 目录号 : GC19459
An activator of sGC
Cas No.:646995-35-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | Aliquots of the platelet suspension are withdrawn before and at various times after addition of spermine NONOate or Cinaciguat and transferred immediately into inactivation buffer (50 mM Tris, 4 mM EDTA, pH 7.4) at 100°C for at least 10 min. When used, 10 μM ODQ is added to the platelets 15 min before addition of spermine NONOate. Purified GC activity is measured at a final concentration of 50 ng/mL in assay buffer (50 mM Tris, 100 μM EDTA, 1 mM NaGTP, 1.3 mM MgCl2, 50 μg/mL BSA, pH 7.4), stimulated with DEA/NO (10 μM) or Cinaciguat (1 μM), enzyme inactivation being performed as with platelets. The levels of cGMP are measured by radioimmunoassay and expressed relative to the amount of protein. Three independent runs are carried out in each experiment and the resulting data presented as means±s.e.mean[1]. |
Animal experiment: | Mice[2] Male and female mice (12 weeks old) are anaesthetized with isoflurane, 0.5 cm of the tail tip is removed with a sharp razor blade, and the tail tip is immediately put into fresh pre-warmed PBS of 37°C. The latency until the tail stopped bleeding is visually scored and recorded with a chronometer by an observer blinded to the genotype. Systolic BP (SBP) and heart rate (HR) are measured non-invasively in awake mice by tail-cuff using a Hatteras MC4000 Blood Pressure Analysis System. Mice are habituated to the BP measurement device for 7 days. To determine basal BP, mice are measured for 15 consecutive cycles per day during 5 days. L-NAME (100 mg/kg), SNP (1.5 mg/kg), DETA-NO (60 mg/kg), BAY 41-2772 (4 mg/kg), Cinaciguat (30 μg/kg) and the vehicle controls (PBS or for the BAY-compounds 20% Cremophor+20% diethylene-glycol-monoethyl-ether in PBS) are all administered IP. After SNP administration, SBP measurements are recorded from 5 to 15 min post injection, for L-NAME and DETA-NO recordings are made from 1 to 25 min post injection and for BAY-compounds recordings are made from 10 to 25 min post injection. |
References: [1]. Roy B, et al. Probing the presence of the ligand-binding haem in cellular nitric oxide receptors. Br J Pharmacol. 2008 Apr;153(7):1495-504. | |
Cinaciguat hydrochloride is a potent soluble guanylate cyclase (GC) activator with EC50 of 15 nM in platelets.
In platelets, Cinaciguat (BAY 58-2667) is a potent GC activator (EC50 15 nM) but the maximum effect is only about 1% of that achievable with NO. Concentration-response curves for Cinaciguat are constructed after 1 min exposure in the presence of sildenafil. Without ODQ, the EC50 is 18 nM, and in the presence of ODQ the potency of Cinaciguat is not significantly different, the EC50 being 13 nM. The potency of Cinaciguat in platelets (EC50 15 nM) is very similar to estimates made on purified recombinant GC. Cinaciguat at a maximally effective concentration of 1 μM stimulates control GC activity to about 25% of that observed with NO and, contrasting with the stimulation by NO, this level of activity remained constant as the proportion of ODQ-pretreated GC is increased[1].
Administration of Cinaciguat decreased BP and increased HR in both apo-sGC mice and WT mice. In fact, the BP-lowering effect of Cinaciguat in apo-sGC mice is significantly greater and longer lasting than in WT mice. In addition, Cinaciguat decreased BP in apo-sGC mice at concentrations that did not affect BP in WT mice. Furthermore, the IC50 values for Cinaciguat-induced ex vivorelaxation of precontracted aortas are threefold lower in apo-sGC mice than in WT mice (IC50=0.2 nM and 0.7 nM, respectively). Together, our results suggest that sGC activators like Cinaciguat but not sGC stimulators like BAY 41-2272 activate apo-sGC. In addition, the observation that Cinaciguat can modulate vasorelaxation and BP in WT mice suggests that even in healthy mice, a subset of the available sGC pool is haem-free and responsive to sGC activators[2].
[1]. Roy B, et al. Probing the presence of the ligand-binding haem in cellular nitric oxide receptors. Br J Pharmacol. 2008 Apr;153(7):1495-504. [2]. Thoonen R, et al. Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice. Nat Commun. 2015 Oct 7;6:8482.
| Cas No. | 646995-35-9 | SDF | |
| 别名 | BAY 58-2667 hydrochloride | ||
| Canonical SMILES | OC(C(C=C1)=CC=C1CN(CCCCC(O)=O)CCC(C=CC=C2)=C2OCC(C=C3)=CC=C3CCC4=CC=CC=C4)=O.[H]Cl | ||
| 分子式 | C36H40ClNO5 | 分子量 | 602.16 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH7.2) (1:1): 0.5 mg/ml,Ethanol: 5 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6607 mL | 8.3034 mL | 16.6069 mL |
| 5 mM | 0.3321 mL | 1.6607 mL | 3.3214 mL |
| 10 mM | 0.1661 mL | 0.8303 mL | 1.6607 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
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