| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
Targets the bradykinin B1 receptor (B1R) with high selectivity and potency. Unlike the B2 receptor, the B1 receptor is generally not constitutively expressed but is induced under inflammatory conditions. R715 acts as a competitive antagonist, blocking the effects of B1 receptor agonists like des-Arg9-bradykinin and Lys-des-Arg9-bradykinin.
|
|---|---|
| ln Vitro |
In vitro, R715 is characterized by its potent and selective antagonism of the bradykinin B1 receptor. Its high pA2 value of 8.49 confirms its ability to block B1R activation at nanomolar concentrations, while its lack of activity at B2 receptors ensures the specific dissection of B1R-mediated pathways in tissue and cell-based studies.
|
| ln Vivo |
R715 has demonstrated in vivo efficacy in animal models. It significantly attenuates the hyperalgesic effect (increased pain sensitivity) developed in Streptozotocin (STZ)-diabetic mice. This result confirms the functional role of the B1 receptor in the development of diabetic neuropathic pain and highlights the utility of R715 as a pharmacological tool.
|
| Enzyme Assay |
Non-cell radioligand binding assays are performed using membranes from cells that overexpress the human bradykinin B1 receptor. The membranes are incubated with a radio-labeled B1 receptor agonist (e.g., [3H]Lys-des-Arg9-bradykinin) and increasing concentrations of R715. Bound radioactivity is separated by filtration and counted to determine the antagonist‘s affinity (Ki) using Scatchard analysis.
|
| Cell Assay |
Functional cell-based assays for B1 antagonism are conducted in cells that endogenously or recombinantly express the B1 receptor, such as IMR-90 human lung fibroblasts. Cells are loaded with a calcium-sensitive fluorescent dye. After a pre-incubation step with R715, the cells are stimulated with a B1 receptor agonist (e.g., des-Arg9-bradykinin). The inhibition of agonist-induced calcium flux by the antagonist is measured to confirm its activity.
|
| Animal Protocol |
In the Streptozotocin (STZ)-diabetic mouse model, diabetes is induced by a single intraperitoneal injection of STZ. After a few weeks, when hyperalgesia is established, R715 is administered to the animals. Its effect on pain sensitivity is then assessed by standard behavioral tests such as the hot plate test or von Frey filaments for mechanical allodynia, demonstrating its anti-hyperalgesic effect.
|
| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for R715 is not publicly available. As a peptide antagonist with a molecular weight of 1140.33, it is not orally bioavailable and is typically administered via injection. However, it is noted to be metabolically stable, suggesting it has a longer duration of action in vivo compared to other peptide antagonists that are rapidly degraded.
|
| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for R715. As a selective B1 receptor antagonist, it is expected to be well-tolerated in acute experimental settings. Its use in animal models, such as the diabetic neuropathy model, did not report any adverse effects, but dedicated toxicity studies are not available.
|
| References | |
| Additional Infomation |
R715 is a research-grade peptide and is not approved for clinical use. It is a well-established and highly selective pharmacological tool for studying the bradykinin B1 receptor, which is a major target for the development of novel analgesics for chronic pain conditions such as diabetic neuropathy and inflammatory pain.
|
| Molecular Formula |
C57H81N13O12
|
|---|---|
| Molecular Weight |
1140.33
|
| Exact Mass |
1139.61
|
| CAS # |
185052-09-9
|
| PubChem CID |
5311397
|
| Sequence |
Ac-Lys-Arg-Pro-Pro-Gly-Phe-Ser-{d-βNal}-IleAc-KRPPGFS-{d-βNal}-I
|
| SequenceShortening |
Ac-KRPPGFS-{d-βNal}-I
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.67
|
| Hydrogen Bond Donor Count |
12
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
31
|
| Heavy Atom Count |
82
|
| Complexity |
2210
|
| Defined Atom Stereocenter Count |
9
|
| SMILES |
CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@@H](CC1=CC2=CC=CC=C2C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)CNC(=O)[C@@H]4CCCN4C(=O)[C@@H]5CCCN5C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)NC(=O)C
|
| InChi Key |
DOSXOGUJJBDRGQ-VUBDHFCFSA-N
|
| InChi Code |
InChI=1S/C57H81N13O12/c1-4-34(2)48(56(81)82)68-51(76)43(31-37-23-24-38-17-8-9-18-39(38)29-37)66-52(77)44(33-71)67-50(75)42(30-36-15-6-5-7-16-36)64-47(73)32-62-53(78)45-21-13-27-69(45)55(80)46-22-14-28-70(46)54(79)41(20-12-26-61-57(59)60)65-49(74)40(63-35(3)72)19-10-11-25-58/h5-9,15-18,23-24,29,34,40-46,48,71H,4,10-14,19-22,25-28,30-33,58H2,1-3H3,(H,62,78)(H,63,72)(H,64,73)(H,65,74)(H,66,77)(H,67,75)(H,68,76)(H,81,82)(H4,59,60,61)/t34-,40-,41-,42-,43+,44-,45-,46-,48-/m0/s1
|
| Chemical Name |
(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-methylpentanoic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~87.7 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (2.19 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (2.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8769 mL | 4.3847 mL | 8.7694 mL | |
| 5 mM | 0.1754 mL | 0.8769 mL | 1.7539 mL | |
| 10 mM | 0.0877 mL | 0.4385 mL | 0.8769 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
