| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
BEC HCl (S-(2-boronoethyl)-L-cysteine) is a specific competitive inhibitor of the binuclear manganese metalloenzyme arginase. [3]
|
|---|---|
| ln Vitro |
Using hemihedral completely twinned crystals, the X-ray crystal structure of the arginase-BEC complex has been established at a resolution of 2.3 Å. The complex's structure demonstrates that a metal-bridging hydroxide ion nucleophilically attacks the boronic acid moiety, resulting in the formation of a tetrahedral borate anion that bridges the dinuclear manganese cluster. This mimics the tetrahedral intermediate and its flanking ions in the transition state of the arginine hydrolysis reaction [2].
Treatment of primary mouse tracheal epithelial cells with BEC HCl at concentrations of 0.5 mM or 1 mM for 24 hours significantly inhibited arginase activity in vitro. The inhibitory effect was more robust when the assay was performed in the presence of lower concentrations of the substrate L-arginine. [3] |
| ln Vivo |
Increased S-nitrosylated and nitrated proteins are seen in the lungs of inflamed mice after the arginase inhibitor BEC is administered. This decreases arginase activity and alters NO homeostasis. BECs promote mucus metaplasia, NF-κB DNA binding, mRNA production of the NF-κB-driven chemokine genes CCL20 and KC, and perivascular and peribronchiolar lung inflammation. They also cause further increases in airway hyperresponsiveness [3].
In a mouse model of allergic airway disease (OVA-sensitized and challenged BALB/c mice), oropharyngeal aspiration of BEC HCl (0.30 mmol/L in 40 μL PBS) 2 hours after the last OVA challenge enhanced peribronchiolar and perivascular lung inflammation, mucus metaplasia, and airways hyperresponsiveness compared to PBS-treated controls. [3] BEC HCl treatment also led to increased NF-κB DNA binding and mRNA expression of NF-κB-dependent inflammatory genes (KC and CCL20) in lung tissue, along with elevated levels of protein S-nitrosylation and tyrosine nitration. [3] Treatment with BEC HCl significantly inhibited arginase activity in bronchoalveolar lavage (BAL) cells from inflamed mice at 24 and 48 hours post-administration. [3] OVA-specific IgE levels in plasma were decreased in BEC HCl-treated OVA/OVA mice compared to PBS-treated OVA/OVA controls. [3] Levels of the Th2 cytokine IL-4 in BAL fluid were decreased in inflamed mice exposed to BEC HCl compared to PBS controls. [3] |
| Enzyme Assay |
Arginase activity was evaluated in inflammatory cells obtained from bronchoalveolar lavage (BAL) or in lysates from primary mouse tracheal epithelial cells. The assay measures urea production by arginase from its substrate L-arginine. Urea concentration is determined spectrophotometrically at 540 nm using a standard curve generated with urea. Results are expressed as nanograms of urea per microgram of protein. [3]
To demonstrate inhibition by BEC HCl, primary mouse tracheal epithelial cells were cultured and treated with 0.5 mM or 1 mM BEC HCl for 24 hours. The arginase assay was then performed with different concentrations of L-arginine as indicated. [3] |
| Animal Protocol |
Animal/Disease Models: C57BL/6J wild-type mice, arginase 2-deficient mice (Arg2-/-), arginase 1 and arginase 2-deficient mice (Arg1-/-Arg2-/ -), NOX2-deficient mice (NOX2-/-
Doses: 20 mg/kg. Route of Administration: 1 hour before LPS injection, intravenous (iv) (iv)injection of 0.9% saline. Experimental Results: BEC Dramatically diminished glial cells (72% reduction) and VEGF expression in macrophages/microglia (87% reduction). A mouse model of allergic airway disease was established using 6- to 8-week-old female BALB/c mice. Mice were sensitized by intraperitoneal (i.p.) injection of 20 μg OVA adsorbed to 2.25 mg alum on days 0 and 7. They were challenged via aerosol with 1% OVA in PBS for 30 minutes on days 14-16. Two hours after the last OVA challenge, mice were anesthetized with isoflurane and subjected to oropharyngeal aspiration of either BEC HCl (0.30 mmol/L in PBS) or PBS alone in a volume of 40 μL. Mice were euthanized 48 hours after the last OVA challenge (day 18) for sample collection. [3] Respiratory mechanics and airway hyperresponsiveness were assessed in anesthetized, mechanically ventilated mice using the forced oscillation technique. Measurements (Newtonian resistance, tissue resistance/airflow heterogeneity, airway closure/elastance) were recorded in response to ascending doses of methacholine. [3] |
| References |
|
| Additional Infomation |
BEC HCl is a borate-based arginine analog that, once synthesized, acts as a specific competitive inhibitor of arginase. Previously, it has been used to investigate the mechanism by which nitric oxide synthase (NOS) regulates NO production by competing for the endogenous L-arginine pool. [3]
In the context of allergic airway disease, the inhibitory effect of BEC HCl on arginase alters nitric oxide (NO) homeostasis, leading to increased levels of protein S-nitrosylation (potentially beneficial) and protein tyrosine nitration (potentially harmful), which may contribute to the observed increased inflammation and hyperresponsiveness. [3] This study suggests that the pro-inflammatory effect of BEC HCl in this model may be related to the generation of reactive nitrogen species (RNS) after arginase inhibition, rather than a simple increase in bioavailable NO. [3] |
| Molecular Formula |
C5H13BCLNO4S
|
|---|---|
| Molecular Weight |
229.482
|
| Exact Mass |
229.035
|
| CAS # |
222638-67-7
|
| Related CAS # |
222638-67-7 (HCl);63107-40-4;
|
| PubChem CID |
91826515
|
| Appearance |
White to yellow solid powder
|
| LogP |
0.106
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
13
|
| Complexity |
145
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
B(CCSC[C@@H](C(=O)O)N)(O)O.Cl
|
| InChi Key |
GHPYJLCQYMAXGG-WCCKRBBISA-N
|
| InChi Code |
InChI=1S/C5H12BNO4S.ClH/c7-4(5(8)9)3-12-2-1-6(10)11;/h4,10-11H,1-3,7H2,(H,8,9);1H/t4-;/m0./s1
|
| Chemical Name |
(2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid;hydrochloride
|
| Synonyms |
S-(2-boronoethyl)-L-cysteine BEC HCl
|
| 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 (e.g. under nitrogen), 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) |
H2O : ~50 mg/mL (~217.87 mM)
DMSO : ~50 mg/mL (~217.87 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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 (10.89 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (10.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 140 mg/mL (610.05 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3577 mL | 21.7884 mL | 43.5768 mL | |
| 5 mM | 0.8715 mL | 4.3577 mL | 8.7154 mL | |
| 10 mM | 0.4358 mL | 2.1788 mL | 4.3577 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03389022 | UNKNOWN STATUS | Drug: Ketamine Drug: Saline Drug: Ketamine |
Bariatric Surgery Candidate Pain, Postoperative |
Lithuanian University of Health Sciences | 2015-07-22 | Phase 4 |
| NCT04483024 | COMPLETED | Dietary Supplement: Collagen hydrolysate and chicken extract |
Knee Osteoarthritis Muscle Loss |
Shan May Yong | 2018-12-01 | Phase 1 |
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
