Cinaciguat (formerly also known as BAY582667 or BAY58-2667) is a novel and potent activator of soluble guanylate cyclase (sGC) used for acute decompensated heart failure. In a rat model of type-1 diabetes mellitus, ciprofloxacin avoids cardiac dysfunction. Cinaciguat has no direct effects on the relaxation and contractility of cardiac myocytes from rats that are normal. By reducing the migration and proliferation of vascular smooth muscle cells following arterial injury, cipracapat inhibits the formation of neointima.
Physicochemical Properties
| Molecular Formula | C36H39NO5 |
| Molecular Weight | 565.69856 |
| Exact Mass | 565.282 |
| Elemental Analysis | C, 76.43; H, 6.95; N, 2.48; O, 14.14 |
| CAS # | 329773-35-5 |
| Related CAS # | Cinaciguat hydrochloride; 646995-35-9 |
| PubChem CID | 9808022 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 731.0±60.0 °C at 760 mmHg |
| Flash Point | 395.9±32.9 °C |
| Vapour Pressure | 0.0±2.5 mmHg at 25°C |
| Index of Refraction | 1.614 |
| LogP | 8.14 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 17 |
| Heavy Atom Count | 42 |
| Complexity | 767 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | OC(C(C=C1)=CC=C1CN(CCCCC(O)=O)CCC(C=CC=C2)=C2OCC(C=C3)=CC=C3CCC4=CC=CC=C4)=O |
| InChi Key | WPYWMXNXEZFMAK-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C36H39NO5/c38-35(39)12-6-7-24-37(26-30-19-21-33(22-20-30)36(40)41)25-23-32-10-4-5-11-34(32)42-27-31-17-15-29(16-18-31)14-13-28-8-2-1-3-9-28/h1-5,8-11,15-22H,6-7,12-14,23-27H2,(H,38,39)(H,40,41) |
| Chemical Name | 4-[[4-carboxybutyl-[2-[2-[[4-(2-phenylethyl)phenyl]methoxy]phenyl]ethyl]amino]methyl]benzoic acid |
| Synonyms | BAY 582667; BAY-582667; BAY582667; BAY 58-2667; BAY-58-2667; BAY58-2667; Cinaciguat HCl; Cinaciguat hydrochloride |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | H3 receptor ( Ki = 0.16 nM ) |
| ln Vitro | Cinaciguat (10 μM) significantly enhances intracellular cGMP production. Cinaciguat has no dose-dependent effects on cell contraction and induces transient changes [2]. |
| ln Vivo | Cinaciguat (10 mg/kg/day, po) treatment of diabetic cholesterol did not affect blood pressure levels but resulted in reduced water recognition. Cinaciguat treatment reduces diabetes-associated oxidation, prevents DM-associated alterations in NO-sGC-cGMP-PKG signaling, and reduces DM-associated cardiac hypertrophy and cellular sterility [1]. Cinaciguat (1-10-100 nM) caused concentration contraction in smooth muscle strips of both WT and apo-sGC mice, but PGF2α had no effect on the relative activity of gastrointestinal smooth muscle strips of WT or apo-sGC [3]. |
| Animal Protocol | Rats are randomized into four groups after DM is confirmed: vehicle-treated control, cinaciguat-treated control, vehicle-treated diabetic, and cinaciguat-treated diabetic groups. Treatment begins immediately upon DM confirmation and lasts for 8 weeks. The animals are given either a 0.5% methylcellulose vehicle or the sGC activator cinaciguat in suspension p.o. (10 mg/kg/day). Daily water consumption is measured and water bottles are filled with the same volume of fresh tap water each morning. To avoid water spilling from the bottles, animal cages are handled carefully and are not moved after the bottles are replaced. Once every two days, the animals' body weight is measured, and the cinaciguat dosage is modified accordingly. |
| References |
[1]. The soluble guanylate cyclase activator cinaciguat prevents cardiac dysfunction in a rat model of type-1 diabetes mellitus. Cardiovasc Diabetol. 2015 Oct 31;14:145. [2]. The soluble guanylate cyclase stimulator riociguat and the soluble guanylate cyclase activator cinaciguat exert no direct effects on contractility and relaxation of cardiac myocytes from normal rats. Format: AbstractSend to Eur J Pharmaco. [3]. Influence of cinaciguat on gastrointestinal motility in apo-sGC mice. Neurogastroenterol Motil. 2014 Nov;26(11):1573-85. |
| Additional Infomation |
Cinaciguat is a benzoic acid that is 4-(aminomethyl)benzoic acid in which the amino group is substituted by 4-carboxybutyl and 2-(2-{[4-(2-phenylethyl)benzyl]oxy}phenyl)ethyl groups. It is a soluble guanylate cyclase activator, used for the treatment of acute decompensated heart failure. It has a role as a vasodilator agent, a soluble guanylate cyclase activator and an antihypertensive agent. It is a member of benzoic acids, a tertiary amino compound, an aromatic ether and a dicarboxylic acid. Cinaciguat is under investigation in clinical trial NCT01067859 (A Phase Iib Study to Investigate the Efficacy and Tolerability of Lower Doses Cinaciguat (25 ΜG/h, 10 ΜG/h) Given Intravenously to Patients With Acute Decompensated Chronic Congestive Heart Failure (ADHF)). |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~66 mg/mL (~198.6 mM) Water: ~66 mg/mL Ethanol: ~66 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.42 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7677 mL | 8.8386 mL | 17.6772 mL | |
| 5 mM | 0.3535 mL | 1.7677 mL | 3.5354 mL | |
| 10 mM | 0.1768 mL | 0.8839 mL | 1.7677 mL |