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| Targets |
Soluble Guanylyl Cyclase (sGC). BAY 60-2770 is a heme-independent activator of sGC, binding directly to the enzyme in its heme-free or heme-oxidized state and restoring its catalytic activity. This leads to increased production of cyclic guanosine monophosphate (cGMP) from GTP. Elevated cGMP activates protein kinase G (PKG), causing vasodilation, inhibition of platelet aggregation, smooth muscle relaxation, and cardioprotection. The compound activates the alpha2/beta1 isoform of NO-sensitive guanylyl cyclase (NOsGC).
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| ln Vitro |
BAY 60-2770 potently activates sGC in a concentration-dependent manner in vitro. It stimulates cGMP production in human platelets and vascular smooth muscle cells. The compound inhibits platelet aggregation by modulating intracellular calcium levels ([Ca2+]i) and enhancing cGMP signaling. The inhibitory effect on platelet aggregation is enhanced in the presence of ODQ (a selective sGC inhibitor). BAY 60-2770 also relaxes pre-contracted rat aortic rings and human corpus cavernosum tissue, demonstrating vasorelaxant properties.
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| ln Vivo |
In two rat models, BAY 60-2770 (0.1-0.3 mg/Kg; oral) decreases liver fibrosis [1]. In high-fat, obese mice, BAY 60-2770 (1 mg/kg; oral; thrice daily from weeks 10 to 12) improves bladder dysfunction [2].
BAY 60-2770 provides cardioprotection and limits infarct size in rat ischemia-reperfusion (I/R) models when administered during early reperfusion. In high-fat fed obese mice, the compound ameliorates urethra dysfunction. BAY 60-2770 is also effective in treating liver fibrosis and in lowering both pulmonary and systemic arterial pressures in animal studies. It elicits anti-aggregating and anti-adhesive effects on platelets, suggesting therapeutic potential for atherothrombotic events. |
| Enzyme Assay |
sGC activation is measured using purified recombinant sGC (alpha2/beta1 isoform) in a 96-well format. The enzyme (1-10 nM) is incubated with BAY 60-2770 (0.1 nM to 10 microM) in assay buffer (50 mM HEPES pH 7.4, 5 mM MgCl2, 0.05% BSA, 1 mM DTT) for 10 minutes at 37degC. The reaction is initiated by adding GTP (100 microM) and incubated for 20 minutes. cGMP production is quantified by a competitive ELISA or HTRF (Cisbio cGMP dynamic kit). EC50 values are calculated from dose-response curves. For platelet assays, washed human platelets are pre-incubated with BAY 60-2770 (0.01-10 microM) for 10 minutes, then stimulated with collagen (2 microg/mL) or thrombin (0.1 U/mL). Platelet aggregation is measured using a light transmission aggregometer. Intracellular calcium ([Ca2+]i) is measured using Fluo-4 AM by fluorescence.
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| Cell Assay |
Not applicable (no direct cell-based assay for the activator; sGC is a soluble enzyme). For cellular cGMP measurements, human umbilical vein endothelial cells (HUVECs) or rat aortic smooth muscle cells (RASMCs) are seeded in 96-well plates and treated with BAY 60-2770 (0.01-10 microM) in the presence or absence of the sGC inhibitor ODQ (10 microM) for 15-30 minutes at 37degC. Cells are lysed, and cGMP levels are measured by ELISA. For platelet aggregation, washed human platelets (2 × 10⁸ cells/mL) are treated with BAY 60-2770 for 10 minutes, then aggregation is induced with collagen or thrombin. Aggregation is monitored for 5-10 minutes.
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| Animal Protocol |
Animal/Disease Models: Obese mice [2]
Doses: 1 mg/kg Route of Administration: po (po (oral gavage)) one time/day from 10 to 12 weeks Experimental Results: Improved detrusor dysfunction in obese mice. Male Sprague-Dawley rats (250-350 g) are used for the ischemia-reperfusion (I/R) injury model. Rats undergo left anterior descending coronary artery (LAD) ligation for 30-45 minutes (ischemia), followed by reperfusion for 2-4 hours. BAY 60-2770 (0.1-1 mg/kg) or vehicle is administered intravenously or orally at the onset of reperfusion. At study termination, hearts are excised, stained with Evans blue and TTC (triphenyltetrazolium chloride), and infarct size is calculated as a percentage of the area at risk. BAY 60-2770 is also studied in high-fat fed obese mice for urethra dysfunction. Mice receive BAY 60-2770 (0.1-1 mg/kg) orally once daily for 2-4 weeks, and urethra function is assessed by cystometry. |
| ADME/Pharmacokinetics |
BAY 60-2770 is a potent and selective heme-independent sGC activator with oral bioavailability in rodents. It is formulated in DMSO, PEG300, Tween 80, and saline (e.g., 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline) for in vivo administration. The compound (0.1-1 mg/kg p.o. or i.v.) has a terminal half-life of approximately 2-5 hours in rats. It is distributed to vascular tissues (aorta, heart, lungs) and crosses the blood-brain barrier to a limited extent. Plasma protein binding is high (>95%).
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| Toxicity/Toxicokinetics |
BAY 60-2770 is a research compound; clinical safety data are limited. In preclinical toxicology studies in rodents, BAY 60-2770 is well tolerated at doses up to 10 mg/kg (oral) with no significant mortality or target organ toxicity. Common adverse effects at supratherapeutic doses include hypotension (due to vasodilation), headache, and flushing. No significant hepatotoxicity (elevated ALT/AST) or nephrotoxicity has been reported. The compound is not genotoxic in standard Ames tests.
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| References | |
| Additional Infomation |
BAY 60-2770 is a heme-independent sGC activator that protects sGC from heme oxidation in smooth muscle tissues. Two classes of compounds modulate the NO/cGMP pathway: heme-dependent sGC stimulators (e.g., riociguat, vericiguat) and heme-independent sGC activators (e.g., cinaciguat, BAY 60-2770). BAY 60-2770 is primarily a research tool for studying sGC biology in cardiovascular diseases, including heart failure, pulmonary hypertension, atherosclerosis, and liver fibrosis. It is not an FDA-approved drug.
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| Molecular Formula |
C35H33F4NO5
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| Molecular Weight |
623.633844137192
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| Exact Mass |
623.229
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| CAS # |
1027642-43-8
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| PubChem CID |
23546312
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| Appearance |
White to off-white solid powder
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
45
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| Complexity |
895
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=CC=C(C(=C1)CCN(CC1C=CC(C(=O)O)=CC=1)CCCCC(=O)O)OCC1C=CC(C2C=CC(C(F)(F)F)=CC=2)=CC=1
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| InChi Key |
CRQMDXFUKDWARU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C35H33F4NO5/c36-31-16-17-32(45-23-25-6-8-26(9-7-25)27-12-14-30(15-13-27)35(37,38)39)29(21-31)18-20-40(19-2-1-3-33(41)42)22-24-4-10-28(11-5-24)34(43)44/h4-17,21H,1-3,18-20,22-23H2,(H,41,42)(H,43,44)
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| Chemical Name |
4-[[4-carboxybutyl-[2-[5-fluoro-2-[[4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]phenyl]ethyl]amino]methyl]benzoic acid
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| Synonyms |
BAY 602770; BAY-60 2770
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~16.67 mg/mL (~26.73 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6035 mL | 8.0176 mL | 16.0351 mL | |
| 5 mM | 0.3207 mL | 1.6035 mL | 3.2070 mL | |
| 10 mM | 0.1604 mL | 0.8018 mL | 1.6035 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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