| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
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| Targets |
Although it only affects a portion of the angiotensin response, L-162,389 increases phosphatidylinositol turnover. L-162,389 has an IC50 value of 105 nM, making it an angiotensin antagonist[1].
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| ln Vitro |
Although it only affects a portion of the angiotensin response, L-162,389 increases phosphatidylinositol turnover. L-162,389 has an IC50 value of 105 nM, making it an angiotensin antagonist[1].
L-162,389 binds with high affinity to the cloned angiotensin AT1 receptor expressed in COS-7 cells, with an IC50 of 7.72 nM in the rat receptor and 3.97 nM in the human receptor as determined by competition against 125I-[Sar1,Leu8]angiotensin II.[1] In COS-7 cells expressing the wild-type rat AT1 receptor, L-162,389 stimulated phosphatidylinositol turnover when applied alone, but only to 7.1 ± 0.5% of the maximal response achieved by angiotensin II. The EC50 for this stimulation was approximately 30 nM.[1] L-162,389 potently inhibited angiotensin II-induced phosphatidylinositol turnover in COS-7 cells expressing the wild-type rat AT1 receptor, acting as an insurmountable antagonist (shifting the angiotensin II dose-response curve to the right and suppressing the maximal response). The IC50 for this inhibition was 1.05 × 10-7 M (105 nM).[1] In the N295D mutant rat AT1 receptor expressed in COS-7 cells, L-162,389 lost its agonistic activity (no clear stimulation observed) but acted as a potent antagonist of angiotensin II-induced phosphatidylinositol turnover, with an IC50 value in the range of 90–180 nM, similar to L-162,313 and L-162,782 in this mutant.[1] |
| ln Vivo |
L-162,389 is described as an angiotensin receptor antagonist in vivo, based on prior studies referenced in the introduction. The specific in vivo experimental data (e.g., blood pressure effects) for L-162,389 are not provided in this paper.[1]
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| Enzyme Assay |
Radioligand competition binding assays were performed to determine the affinity of L-162,389 for wild-type and mutant AT1 receptors. Transfected COS-7 cells were washed and incubated for 24 hours at 4°C with 50 pM 125I-[Sar1,Leu8]angiotensin II and varying concentrations of unlabeled L-162,389 in a Tris buffer (25 mM Tris, 5 mM MgCl2, 140 mM NaCl, pH 7.4). Binding data were analyzed by nonlinear regression.[1]
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| Cell Assay |
Phosphatidylinositol turnover assays were conducted in COS-7 cells transiently expressing wild-type or mutant rat AT1 receptors. Cells were cultured for 24 hours in inositol-free medium containing myo-[3H]inositol. After washing, cells were pre-incubated for 30 min at 37°C in buffer containing LiCl. For agonist mode, cells were incubated with varying concentrations of L-162,389 alone for 1 hour. For antagonist mode, cells were pre-incubated with L-162,389 for 30 min before adding a submaximal dose of angiotensin II and incubating for another hour. Reactions were stopped with perchloric acid. After centrifugation and neutralization, [3H]inositol phosphates were separated by anion exchange chromatography and quantified.[1]
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| ADME/Pharmacokinetics |
The literature provided [1] does not contain information on the absorption, distribution, metabolism, excretion, half-life or oral bioavailability of L-162,389.
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| Toxicity/Toxicokinetics |
The provided literature [1] does not contain information on the toxicity, lethal dose, organ toxicity, drug interactions, or plasma protein binding of L-162,389.
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| References | |
| Additional Infomation |
L-162,389 is a bibenzamide nonpeptide compound. [1]
It differs from the agonist L-162,782 in structure only by a single methyl group, but it exhibits primarily antagonistic activity in vivo and in functional assays against wild-type receptors. [1] The A104V mutation at the top of transmembrane segment III weakens its binding to the AT1 receptor (affinity reduced by 26-fold), while mutations such as T287A and N294A in transmembrane segment VII also have a slight effect on its binding. [1] This study demonstrates that small chemical modifications (single methyl group) or specific point mutations (e.g., N295D) on the receptor can significantly alter the agonist potency of such compounds without significantly affecting their binding affinity. [1] |
| Molecular Formula |
C31H38N4O4S
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|---|---|
| Molecular Weight |
562.722826480865
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| Exact Mass |
562.261
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| CAS # |
169281-53-2
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| PubChem CID |
9850834
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.607
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| LogP |
7.38
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
40
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| Complexity |
904
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(OCCCC)(=O)NS(C1=CC=C(CCC)C=C1C1=CC=C(CN2C3=NC(C)=CC(C)=C3N=C2CC)C=C1)(=O)=O
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| InChi Key |
MLGCITBDCGSKQS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H38N4O4S/c1-6-9-17-39-31(36)34-40(37,38)27-16-13-23(10-7-2)19-26(27)25-14-11-24(12-15-25)20-35-28(8-3)33-29-21(4)18-22(5)32-30(29)35/h11-16,18-19H,6-10,17,20H2,1-5H3,(H,34,36)
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| Chemical Name |
butyl N-[2-[4-[(2-ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-yl)methyl]phenyl]-4-propylphenyl]sulfonylcarbamate
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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 | 1.7771 mL | 8.8854 mL | 17.7708 mL | |
| 5 mM | 0.3554 mL | 1.7771 mL | 3.5542 mL | |
| 10 mM | 0.1777 mL | 0.8885 mL | 1.7771 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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