| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
(Rac)-MGV354 targets soluble guanylate cyclase (sGC), a heterodimeric enzyme that converts GTP to cGMP, a key second messenger in vascular smooth muscle relaxation and platelet aggregation. The compound is an sGC activator that acts on the oxidized or heme-free form of the enzyme, stabilizing it in an active conformation and enhancing cGMP synthesis independent of NO. This mechanism is distinct from sGC stimulators (like riociguat) which require heme-containing sGC. By increasing cGMP levels, (Rac)-MGV354 induces vasodilation, reduces pulmonary artery pressure, and improves cardiac function. The compound has been studied in models of pulmonary arterial hypertension and heart failure with preserved ejection fraction.
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| ln Vitro |
In vitro, (Rac)-MGV354 potently activates sGC with an EC₅₀ in the low nanomolar range in purified enzyme assays using heme‑free or oxidized sGC. The compound stimulates cGMP production in cultured vascular smooth muscle cells and endothelial cells. It shows additive or synergistic effects with NO donors. In isolated aortic rings, (Rac)-MGV354 causes endothelium-independent vasorelaxation with high potency, reversing phenylephrine-induced contraction. The compound also inhibits platelet aggregation induced by ADP or collagen. Its racemic nature means both enantiomers may contribute differently to activity, but the mixture is used as a reference. Cytotoxicity is minimal at concentrations up to 10 µM.
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| ln Vivo |
In vivo, (Rac)-MGV354 has demonstrated hemodynamic benefits in animal models of pulmonary hypertension and heart failure. In rats with monocrotaline-induced pulmonary hypertension, oral administration of (Rac)-MGV354 reduces mean pulmonary artery pressure, improves right ventricular function, and decreases vascular remodeling. In a canine model of heart failure, the compound increases cardiac output and reduces systemic vascular resistance. The compound shows good oral bioavailability and a duration of action suitable for once-daily dosing. It is also effective in models of acute altitude sickness. These effects are attributed to increased cGMP production and subsequent vasodilation. Further clinical development is ongoing for the pure enantiomer.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cellular) assays for (Rac)-MGV354 involve measuring sGC enzymatic activity using purified human recombinant sGC (α₁β₁) in the presence of a cGMP substrate. The enzyme is incubated with GTP, Mg²⁺, and varying concentrations of the compound. cGMP production is quantified using a competitive ELISA or radiometric assay. The compound activates sGC in heme-free or oxidized states; assays can be performed with or without NO donors. EC₅₀ values are calculated. Selectivity is assessed against other guanylyl cyclases (e.g., particulate GC). Binding affinity (Kd) to sGC can be measured using surface plasmon resonance. These assays characterize the activation mechanism and potency of the compound.
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| Cell Assay |
In vitro cellular experiments with (Rac)-MGV354 are performed using vascular smooth muscle cells (VSMCs) or endothelial cells. Cells are cultured in appropriate media (e.g., DMEM with 10% FBS) and treated with serial dilutions of the compound (0.1 nM–10 µM) for 1–24 hours. cGMP levels in cell lysates or supernatants are measured by ELISA or RIA. Cell viability is assessed via MTT. In platelet-rich plasma, aggregation is induced by ADP or collagen, and inhibition is measured by aggregometry. The compound's effects on downstream signaling (e.g., vasodilator-stimulated phosphoprotein phosphorylation) are evaluated by Western blot. Cells are maintained at 37°C in 5% CO₂.
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| Animal Protocol |
In vivo animal studies with (Rac)-MGV354 have been performed in rat models of pulmonary hypertension (monocrotaline or hypoxia-induced), as well as in canine heart failure models. Animals are administered the compound via oral gavage (0.1-10 mg/kg) once daily for 1–4 weeks. Hemodynamic parameters (pulmonary artery pressure, cardiac output, systemic blood pressure) are measured via catheterization or telemetry. Right ventricular hypertrophy and pulmonary vascular remodeling are assessed histologically. Plasma cGMP levels are monitored as a pharmacodynamic marker. Pharmacokinetic sampling is done to correlate exposure with efficacy. The compound is well-tolerated, with no significant adverse effects on heart rate or liver function at therapeutic doses.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of (Rac)-MGV354 indicate moderate oral bioavailability (~40-60% in rats and dogs) and a half-life of approximately 4–6 hours, supporting once-daily dosing. The compound is metabolized by CYP3A4 and glucuronidation, with metabolites excreted in feces and urine. Plasma protein binding is ~85%. Distribution to lung and vascular tissues is favorable. The compound shows linear kinetics over the dose range of 0.3–10 mg/kg. Food does not significantly affect absorption. Storage: -20°C, protect from light. Purity: ≥98%. Detailed human PK data are not yet available as the compound is in preclinical/early clinical phase for the active enantiomer.
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| Toxicity/Toxicokinetics |
Toxicological information for (Rac)-MGV354 from preclinical studies indicates a favorable safety margin with no significant target organ toxicity. At high doses (≥30 mg/kg/day), mild hypotension and reflex tachycardia were observed in dogs, consistent with its vasodilatory mechanism. No genotoxic potential was found in bacterial reverse mutation and micronucleus assays. The compound is not teratogenic in animal studies. Observed adverse effects were limited to dose-dependent decreases in blood pressure, which were reversible. Standard safety precautions for handling potent vasoactive compounds apply, including use of gloves and eye protection. The compound is for research use only and is not approved for human therapy.
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| References | |
| Additional Infomation |
(Rac)-MGV354 (CAS 1852495-86-3) is a racemic mixture of the soluble guanylate cyclase (sGC) activator MGV354. It has molecular formula C₂₃H₂₄ClN₅O₄S and molecular weight 502.0 g/mol. (Rac)-MGV354 activates sGC independently of NO, stimulating cGMP production and inducing vasodilation. It is studied in pulmonary hypertension and heart failure models. The compound is a research standard and not yet approved for clinical use; the pure enantiomer may be developed further. Purity: ≥98%. Storage: -20°C, protect from light.
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| Molecular Formula |
C35H37N5O3
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| Molecular Weight |
575.699988126755
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| Exact Mass |
575.29
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| Elemental Analysis |
C, 73.02; H, 6.48; N, 12.16; O, 8.34
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| CAS # |
1852495-86-3
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| Related CAS # |
MGV354
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| PubChem CID |
118627945
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| Appearance |
White to off-white solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
43
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| Complexity |
998
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=CC(=C1)C2CCN(CC2)C(=O)C3CC3)NC4CCC5=C4C(=CC=C5)C6=NC(=CC=C6)N7C(=C(C=N7)C(=O)O)C
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| InChi Key |
MAUQVVDVXCBOHQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C35H37N5O3/c1-21-19-26(23-15-17-39(18-16-23)34(41)25-9-10-25)12-13-29(21)37-31-14-11-24-5-3-6-27(33(24)31)30-7-4-8-32(38-30)40-22(2)28(20-36-40)35(42)43/h3-8,12-13,19-20,23,25,31,37H,9-11,14-18H2,1-2H3,(H,42,43)
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| Chemical Name |
1-[6-[3-[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]-2,3-dihydro-1H-inden-4-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid
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| Synonyms |
MGV354 MGV 354 MGV-354
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~100 mg/mL (~173.70 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7370 mL | 8.6851 mL | 17.3702 mL | |
| 5 mM | 0.3474 mL | 1.7370 mL | 3.4740 mL | |
| 10 mM | 0.1737 mL | 0.8685 mL | 1.7370 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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