| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg | |||
| 5mg |
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| Other Sizes |
| Targets |
NO-Losartan A targets two mechanisms: (1) the angiotensin II type 1 receptor (AT1R), a G protein-coupled receptor (GPCR) that mediates the vasoconstrictive, pro-inflammatory, and pro-fibrotic effects of angiotensin II. Inhibition of AT1R lowers blood pressure and provides organ protection. (2) Nitric oxide (NO) is a vasodilatory signaling molecule released from the compound, activating soluble guanylyl cyclase (sGC) in vascular smooth muscle, leading to cGMP-mediated vasodilation. Dual targeting may produce additive or synergistic vasodilatory effects.
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| ln Vitro |
No specific in vitro activity data for NO-Losartan A is provided. The losartan parent compound is an AT1R antagonist with IC50 in the low nM range (approximately 1-20 nM for binding and functional inhibition). The NO-releasing moiety is expected to generate nitric oxide, which in standard NO donor assays (e.g., Griess reaction for nitrite/nitrate) would show concentration-dependent NO release. However, specific IC50 values or NO release rates for NO-Losartan A are not available in the summarized literature.
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| ln Vivo |
No specific in vivo data is provided. As a dual-acting antihypertensive agent, NO-Losartan A would be expected to lower blood pressure in animal models of hypertension, such as spontaneously hypertensive rats (SHR) or angiotensin II-infused mice, to a greater extent than losartan alone due to the added vasodilatory effects of NO. The in vivo efficacy would be assessed by radiotelemetry or tail-cuff blood pressure measurement, as well as assessment of end-organ damage (cardiac hypertrophy, renal function). However, specific data for this compound is not reported.
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| Enzyme Assay |
Standard AT1R binding assay: Membrane preparations from cells expressing human AT1R (e.g., CHO-AT1 cells) are incubated with 0.5-2 nM [¹2⁵I]-Sar¹-Ile⁸-angiotensin II ([¹2⁵I]-Ang II) or [3H]-losartan and varying concentrations of NO-Losartan A (0.01-10,000 nM) in 50 mM Tris-HCl buffer (pH 7.4) containing 100 mM NaCl, 5 mM MgCl2, 0.1% BSA at 25degC for 90 minutes. Nonspecific binding is determined using 10 uM unlabeled losartan or Ang II. Bound radioactivity is separated by filtration and counted. Ki values are calculated. Standard NO release assay: NO-Losartan A (10-1000 uM) is incubated in PBS (pH 7.4) at 37degC. At various time points (0-60 minutes), samples are mixed with Griess reagent (sulfanilamide, N-1-naphthylethylenediamine dihydrochloride). Absorbance at 540 nm is measured, and nitrite concentration is determined using a sodium nitrite standard curve.
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| Cell Assay |
Standard cellular AT1R antagonism assay: Cells expressing AT1R (e.g., rat vascular smooth muscle cells, HEK293-AT1 cells) are seeded in 96-well plates. Cells are treated with varying concentrations of NO-Losartan A (0.01-10,000 nM) for 30-60 minutes, then stimulated with angiotensin II (100 nM). Functional responses measured include inositol phosphate (IP) accumulation, intracellular calcium mobilization (Fluo-4 AM), or ERK1/2 phosphorylation (Western blot). The IC50 for inhibition of Ang II-induced responses is calculated. For NO activity, cGMP accumulation can be measured in cGMP-responsive cells (e.g., RFL-6 fibroblasts) following exposure to NO-Losartan A. No specific protocols are provided.
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| Animal Protocol |
No specific animal protocol is provided. A typical in vivo protocol for evaluating antihypertensive agents: 8-10 week old spontaneously hypertensive rats (SHR) are instrumented with telemetry implants or tail-cuff blood pressure monitors. Baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) are measured. NO-Losartan A is administered orally (e.g., 1-30 mg/kg) or intraperitoneally. Blood pressure is measured at various time points (1, 2, 4, 8, 12, 24 hours) post-administration. The percent reduction in SBP/DBP is calculated relative to baseline and compared to vehicle controls and losartan as a comparator. Plasma renin activity, Ang II levels, and NO metabolites (nitrite/nitrate) may be measured. No specific data is reported.
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| ADME/Pharmacokinetics |
No specific PK data is available. As an NO-releasing derivative of losartan, NO-Losartan A would be expected to have PK properties similar to losartan: losartan has oral bioavailability of approximately 33%, a half-life of about 2 hours, and is metabolized to the active metabolite EXP-3174 (which has a longer half-life of 6-9 hours). The NO-releasing moiety may undergo additional metabolic pathways. The compound would be absorbed, distributed, and the NO portion is released spontaneously or metabolically. No specific parameters are provided.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available. Losartan is generally well-tolerated with side effects including dizziness, hypotension, hyperkalemia, and renal impairment. The NO-donating moiety may increase the risk of headache, flushing, and hypotension. Excessive NO release can lead to methemoglobinemia and oxidative stress. As a research compound, it should be handled with standard laboratory safety precautions. Not for human consumption.
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| References | |
| Additional Infomation |
NO-Losartan A is a nitric oxide (NO)-releasing derivative of losartan, an angiotensin II type 1 receptor antagonist. This dual-acting compound is designed to produce enhanced vasodilation and antihypertensive effects via AT1R blockade and NO-mediated sGC activation. For research use only in cardiovascular pharmacology and hypertension studies. Not for human therapeutic applications.
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| Molecular Formula |
C30H28CLN7O5
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|---|---|
| Molecular Weight |
602.04
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| Exact Mass |
601.184
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| CAS # |
791122-48-0
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| PubChem CID |
10371403
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| Appearance |
Typically exists as solids at room temperature
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
818.4±75.0 °C at 760 mmHg
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| Flash Point |
448.8±37.1 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
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| Index of Refraction |
1.671
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| LogP |
6.59
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
43
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| Complexity |
891
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(OCC1N(CC2=CC=C(C3=CC=CC=C3C3=NNN=N3)C=C2)C(CCCC)=NC=1Cl)(=O)C1=CC=CC(CO[N+]([O-])=O)=C1
|
| InChi Key |
MWJCPZGVGOVWQZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H28ClN7O5/c1-2-3-11-27-32-28(31)26(19-42-30(39)23-8-6-7-21(16-23)18-43-38(40)41)37(27)17-20-12-14-22(15-13-20)24-9-4-5-10-25(24)29-33-35-36-34-29/h4-10,12-16H,2-3,11,17-19H2,1H3,(H,33,34,35,36)
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| Chemical Name |
[2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methyl 3-(nitrooxymethyl)benzoate
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.6610 mL | 8.3051 mL | 16.6102 mL | |
| 5 mM | 0.3322 mL | 1.6610 mL | 3.3220 mL | |
| 10 mM | 0.1661 mL | 0.8305 mL | 1.6610 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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