![[Des-Arg9]-Bradykinin acetate](/upload/1124/V31274.png)
| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
[Des-Arg9]-Bradykinin acetate acts on Bradykinin B1 receptor (bradykinin receptor type 1) as a selective agonist [1]
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| ln Vitro |
[Des-Arg9]-Bradykininacetate is an agonist of the Bradykinin(B1) receptor. The first class of physiologically active kinins, bradykinin (BK) and lysyl bradykinin (Lys-BK), are mediated by B2 receptors, which are generated in response to kinins by the action of plasma and tissue kallikreins. The B1 receptor mediates the actions of [Des-Arg9]-bradykinin (des-Arg9-BK) and Lys-des-Arg Arg9-BK, respectively, through carboxypeptidase on BK. It is generated as a result of damage to the original precursor. The interaction with Lys-BK produced the second category of bioactive kinins [1].
1. Receptor binding: - [Des-Arg9]-Bradykinin acetate is a selective agonist for B1 receptor with negligible activity at B2 receptor [1] - [Des-Arg9]-Bradykinin acetate induces concentration-dependent contraction of isolated rabbit aorta (pD2 = 8.6) [1] - [Des-Arg9]-Bradykinin acetate increases both mRNA and protein levels of B1 receptor in IMR-90 human lung fibroblasts in a concentration-dependent manner [1] - [Des-Arg9]-Bradykinin acetate enhances contractile responses to inflammatory cytokines (e.g., oncostatin M) in aortic smooth muscle [1] 2. Cellular effects: - [Des-Arg9]-Bradykinin acetate increases intracellular calcium concentration in cells expressing B1 receptors [1] - [Des-Arg9]-Bradykinin acetate induces NF-κB transcription factor activation, leading to B1 receptor upregulation [1] |
| ln Vivo |
1. Cardiovascular effects:
- In LPS-treated rabbits, [Des-Arg9]-Bradykinin acetate causes dose-dependent decrease in blood pressure [1] - In cat pulmonary vasculature, [Des-Arg9]-Bradykinin acetate exerts tone-dependent effects: vasoconstriction under low-tone conditions and vasodilation under elevated-tone conditions [1] - In dog blood pressure assay, the hypotensive response induced by [Des-Arg9]-Bradykinin acetate is antagonized by dual kinin receptor antagonist B9430 [1] 2. Inflammatory responses: - In mouse pleurisy model, [Des-Arg9]-Bradykinin acetate induces dose-dependent increase in vascular permeability (peaking at 1h) and neutrophil influx (peaking at 4h) [1] - In rat paw edema model, [Des-Arg9]-Bradykinin acetate triggers inflammation that is upregulated by bacterial endotoxin [1] - [Des-Arg9]-Bradykinin acetate alters leukocyte infiltration and expression of inflammatory cytokines (TNF-α, IL-6) in inflammatory sites [1] |
| Enzyme Assay |
1. B1 receptor binding assay:
- Membrane preparation from cells expressing human or mouse B1 receptors is performed, followed by incubation with radiolabeled [Des-Arg9]-Bradykinin acetate and increasing concentrations of unlabeled ligand [1] - Scatchard analysis is applied to determine binding affinity (Ki) and receptor density of [Des-Arg9]-Bradykinin acetate [1] 2. Functional calcium mobilization assay: - 293-AEQ17 cells are transfected with B1 receptor cDNA and engineered to express aequorin [1] - [Des-Arg9]-Bradykinin acetate at various concentrations is added to the cells [1] - Luminescence intensity is measured as an indicator of calcium release induced by [Des-Arg9]-Bradykinin acetate [1] |
| Cell Assay |
1. B1 receptor upregulation assay:
- IMR-90 human lung fibroblasts are cultured in serum-free medium [1] - Cells are treated with increasing concentrations of [Des-Arg9]-Bradykinin acetate (0.1-100 nM) for 24h [1] - RNA extraction and RT-PCR analysis are conducted to detect B1 receptor mRNA levels affected by [Des-Arg9]-Bradykinin acetate [1] - Western blot analysis is performed to quantify B1 receptor protein expression regulated by [Des-Arg9]-Bradykinin acetate [1] 2. Contractility assay in isolated rabbit aorta: - Aorta rings are suspended in organ baths containing Krebs-Henseleit solution (37°C, 95% O2/5% CO2) [1] - [Des-Arg9]-Bradykinin acetate is added cumulatively at concentrations ranging from 10^-10 to 10^-6 M [1] - Isometric tension is measured with force transducers to evaluate the contractile effect of [Des-Arg9]-Bradykinin acetate [1] |
| Animal Protocol |
1. Blood pressure measurement in rabbits:
- Rabbits are anesthetized with urethane (1.2g/kg, i.p.) [1] - Carotid artery is catheterized for blood pressure monitoring [1] - [Des-Arg9]-Bradykinin acetate is injected via femoral vein at doses of 0.1-10 μg/kg [1] - Changes in mean arterial pressure are recorded to assess the cardiovascular effect of [Des-Arg9]-Bradykinin acetate [1] 2. Mouse pleurisy model: - [Des-Arg9]-Bradykinin acetate is administered via intrathoracic injection at doses of 10-100 nmol/site [1] - At specified time points (5min to 48h), pleural fluid is collected for cell counting and cytokine analysis to evaluate the inflammatory response induced by [Des-Arg9]-Bradykinin acetate [1] 3. Dog blood pressure assay: - Dogs are anesthetized prior to the experiment [1] - Dual kinin receptor antagonist B9430 is administered first, followed by [Des-Arg9]-Bradykinin acetate (0.1-10 μg/kg) [1] - Hypotensive responses to [Des-Arg9]-Bradykinin acetate are compared with those induced by bradykinin [1] |
| ADME/Pharmacokinetics |
1. Plasma stability: - [Des-Arg9]-bradykinin acetate is degraded by carboxylpeptidase and aminopeptidase in plasma [1] - [Des-Arg9]-bradykinin acetate has a half-life of approximately 1-2 minutes in human plasma [1] 2. Bioanalysis: - Quantitative analysis of [Des-Arg9]-bradykinin acetate was performed using chemiluminescent enzyme immunoassay (CLEIA), with a detection limit of 27 fmol/ml [1]
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| Toxicity/Toxicokinetics |
1. Acute toxicity: - In rats, high doses (>1 μmol/kg, intravenously) of [Des-Arg9]-bradykinin acetate caused transient hypotension and respiratory distress [1]. 2. Local toxicity: - The inflammatory response induced at the injection site by [Des-Arg9]-bradykinin acetate was dose-dependent and reversible [1].
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| References | |
| Additional Infomation |
1. Biological significance: - [Des-Arg9]-bradykinin acetate is a natural metabolite of bradykinin, formed by the removal of the C-terminal arginine residue [1]. - The B1 receptor (the target of [Des-Arg9]-bradykinin acetate) is usually poorly expressed, but its expression is significantly induced during inflammation, infection, or tissue damage [1]. - [Des-Arg9]-bradykinin acetate is associated with a variety of pathological conditions, including sepsis, pain, and inflammation [1]. 2. Structure-activity relationship: - The deletion of the C-terminal arginine in [Des-Arg9]-bradykinin acetate is crucial for its B1 receptor selectivity [1]. - Lys-[Des-Arg9]-bradykinin is a potent bradykinin acetate analog with enhanced plasma stability [1].
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| Molecular Formula |
C46H65N11O12
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| Molecular Weight |
964.074810743332
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| Exact Mass |
963.481
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| CAS # |
23827-91-0
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| Related CAS # |
[Des-Arg9]-Bradykinin;15958-92-6
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| PubChem CID |
134821694
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
10
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
21
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| Heavy Atom Count |
69
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| Complexity |
1750
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C(=O)(O)C.C(N1CCC[C@H]1C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CO)C(N1CCC[C@H]1C(=O)N[C@H](C(=O)O)CC1C=CC=CC=1)=O)CC1C=CC=CC=1)([C@@H]1CCCN1C(=O)[C@@H](N)CCCNC(N)=N)=O
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| InChi Key |
FLNJLMIOGWOIQM-NHJGMUSQSA-N
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| InChi Code |
InChI=1S/C44H61N11O10.C2H4O2/c45-29(15-7-19-48-44(46)47)40(61)55-22-10-18-35(55)42(63)54-21-8-16-33(54)38(59)49-25-36(57)50-30(23-27-11-3-1-4-12-27)37(58)52-32(26-56)41(62)53-20-9-17-34(53)39(60)51-31(43(64)65)24-28-13-5-2-6-14-28;1-2(3)4/h1-6,11-14,29-35,56H,7-10,15-26,45H2,(H,49,59)(H,50,57)(H,51,60)(H,52,58)(H,64,65)(H4,46,47,48);1H3,(H,3,4)/t29-,30-,31-,32-,33-,34-,35-;/m0./s1
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| Chemical Name |
acetic acid;(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid
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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, avoid exposure to moisture. |
| 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) |
H2O : ~100 mg/mL (~103.73 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 100 mg/mL (103.73 mM) (saturation unknown) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0373 mL | 5.1863 mL | 10.3727 mL | |
| 5 mM | 0.2075 mL | 1.0373 mL | 2.0745 mL | |
| 10 mM | 0.1037 mL | 0.5186 mL | 1.0373 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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