| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Bradykinin B2 receptor (BDKRB2). Labradimil is a selective agonist of the B2 receptor with a Ki of 0.54 nM. Activation of B2 receptors on brain capillary endothelial cells triggers intracellular signaling that leads to transient and reversible opening of the BBB, allowing passage of therapeutic agents into the central nervous system.
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| ln Vitro |
In RBME cells, lobbyadamil raises intracellular free calcium levels [3]. The permeability of human brain microvascular endothelial cell (HMBEC) monolayers is increased by lobradamil (0.01-0.5 nM, 15 minutes)1[4].
In vitro, Labradimil binds to the bradykinin B2 receptor with high affinity (Ki = 0.54 nM). It is more potent and has a longer half-life than native bradykinin. The compound stimulates B2 receptors expressed on brain capillary endothelial cells, leading to activation of downstream signaling pathways that increase BBB permeability. Its specificity for the B2 receptor makes it a valuable tool for studying B2 receptor physiology. |
| ln Vivo |
Rats implanted with RG2 glioma cells exhibit hypotensive effects and increased brain tumor permeability when given lobradamil (2.5 mg/kg bolus plus 10 mg/kg/h for 90 minutes)[2].
In vivo, Labradimil reversibly increases the permeability of the blood-brain barrier. This property has been explored as a strategy to enhance delivery of chemotherapeutic and other therapeutic agents to the brain. The compound's effect on BBB permeability is transient and reversible, minimizing the risk of prolonged disruption of the CNS barrier. Its longer half-life compared to bradykinin allows for more sustained effects. |
| Enzyme Assay |
Cell-free receptor binding assays for Labradimil use membrane preparations from cells expressing recombinant human bradykinin B2 receptors or from tissues rich in B2 receptors. The compound is incubated with a radiolabeled B2 receptor ligand (e.g., [³H]-bradykinin) at varying concentrations for 60-120 minutes at room temperature. Nonspecific binding is determined in the presence of an excess of unlabeled B2 receptor ligand. Bound and free radioactivity are separated by filtration, and Ki values are calculated from competition curves.
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| Cell Assay |
Cellular functional assays for Labradimil use cell lines stably expressing the bradykinin B2 receptor. Cells are seeded in 96-well plates and treated with Labradimil at concentrations ranging from 0.01 nM to 10 μM. Receptor activation is measured by monitoring intracellular calcium mobilization using fluorescent calcium indicators (e.g., Fluo-4) or by measuring inositol phosphate accumulation. EC50 values are determined from dose-response curves. The specificity of the response is confirmed using selective B2 receptor antagonists.
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| Animal Protocol |
Animal/Disease Models: RG2 glioma cells implanted in rats [2]
Doses: 1.5-18 μg/kg Route of Administration: intravenous (iv) (iv)infusion, 0.05 mL/min for 15 minutes Experimental Results: Increased carboplatin uptake in brain tumors (up to 80%) in a dose-dependent manner. In vivo animal studies with Labradimil are typically performed in rodents to assess BBB permeability enhancement. The compound is administered via intravenous or intra-arterial injection at doses ranging from 0.1-10 μg/kg. BBB permeability is measured using Evans blue dye extravasation or by measuring the brain uptake of co-administered tracers (e.g., radiolabeled sucrose or chemotherapeutic agents). The time course of BBB opening is determined by measuring permeability at various time points after administration. Safety studies assess the reversibility of BBB opening and any potential neurotoxicity. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of Labradimil show that it has a longer plasma half-life than native bradykinin, allowing for more sustained biological activity. As a peptide, the compound is administered parenterally (intravenous or intra-arterial) due to poor oral bioavailability. It is metabolized by peptidases in the blood and tissues. Its distribution is primarily to the vascular compartment, with limited penetration into tissues unless the BBB is intentionally disrupted. The compound's rapid clearance requires careful dosing to achieve the desired duration of BBB opening.
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| Toxicity/Toxicokinetics |
Toxicological data for Labradimil are limited to preclinical studies. As a B2 receptor agonist, potential toxicities may include vasodilation, hypotension, and effects on vascular permeability in peripheral tissues. The compound's reversible effect on the BBB minimizes the risk of sustained CNS exposure to potentially harmful substances. Standard toxicology studies would be required for clinical development. At research-grade doses, the compound is handled with standard laboratory precautions.
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| References |
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| Additional Infomation |
Labradimil is a synthetic analog of bradykinin. Labradimil is a potent and specific bradykinin B2 receptor agonist that stimulates B2 receptors expressed on the surface of brain capillary endothelial cells, thereby reversibly increasing the permeability of the blood-brain barrier (BBB). Compared to bradykinin, this drug has higher receptor selectivity, better plasma stability, and a longer half-life. (NCI04)
Drug Indications Investigations are underway for the treatment of brain cancer and pediatric diseases. Labradimil (Lobradimil) was developed as an adjuvant to enhance drug delivery to the brain by transiently opening the BBB. It was investigated in clinical trials for its ability to improve delivery of chemotherapeutic agents to brain tumors. The compound was developed by Alkermes, Inc. and was approved in some regions. Its development represents an important strategy for overcoming the BBB to treat central nervous system disorders. The compound is available for research purposes. |
| Molecular Formula |
C49H75N15O12S
|
|---|---|
| Molecular Weight |
1098.292
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| Exact Mass |
1097.54
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| CAS # |
159768-75-9
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| PubChem CID |
6918284
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| Appearance |
White to off-white solid powder
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| Density |
1.53
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| Index of Refraction |
1.702
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| LogP |
0.795
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| Hydrogen Bond Donor Count |
13
|
| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
29
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| Heavy Atom Count |
77
|
| Complexity |
2080
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| Defined Atom Stereocenter Count |
9
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| SMILES |
COC1=CC=C(C=C1)C[C@@H](CN[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CC3=CC=CS3)NC(=O)CNC(=O)[C@@H]4C[C@H](CN4C(=O)[C@@H]5CCCN5C(=O)[C@H](CCCN=C(N)N)N)O
|
| InChi Key |
IDXCXSCCZNCXCL-XMADEQCMSA-N
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| InChi Code |
InChI=1S/C49H75N15O12S/c1-76-31-14-12-28(13-15-31)21-29(24-57-34(47(74)75)9-3-17-56-49(53)54)59-43(70)37-10-4-18-62(37)45(72)36(27-65)61-41(68)35(23-32-7-6-20-77-32)60-40(67)25-58-42(69)39-22-30(66)26-64(39)46(73)38-11-5-19-63(38)44(71)33(50)8-2-16-55-48(51)52/h6-7,12-15,20,29-30,33-39,57,65-66H,2-5,8-11,16-19,21-27,50H2,1H3,(H,58,69)(H,59,70)(H,60,67)(H,61,68)(H,74,75)(H4,51,52,55)(H4,53,54,56)/t29-,30+,33-,34-,35-,36-,37-,38-,39-/m0/s1
|
| Chemical Name |
(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2S,4R)-1-[(2S)-1-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-methoxyphenyl)propyl]amino]-5-(diaminomethylideneamino)pentanoic acid
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| Synonyms |
DRG0182; DRG 0182; DRG-0182
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | 0.9105 mL | 4.5525 mL | 9.1051 mL | |
| 5 mM | 0.1821 mL | 0.9105 mL | 1.8210 mL | |
| 10 mM | 0.0911 mL | 0.4553 mL | 0.9105 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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