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| 10mg |
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| Targets |
Human arginase I and arginase II. Arginase inhibitor 1 selectively targets both isoforms of the arginase enzyme, which are responsible for catalyzing the hydrolysis of L-arginine to urea and L-ornithine. Inhibition of these enzymes is a therapeutic strategy to increase available L-arginine for nitric oxide synthase, thereby enhancing nitric oxide production and improving vascular function. The compound demonstrates potent inhibitory activity against recombinant human arginase I and II in enzymatic assays. Its selectivity for arginase over other related enzymes makes it a valuable tool for studying the role of arginase in various physiological and pathological processes, particularly those involving the cardiovascular system and immune response.
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| ln Vitro |
Arginase inhibitor 1 is active in a recombinant cell assay overexpressing human arginase I (CHO cells) and inhibits human arginase I and II with IC50 values of 223±22.3 and 509±85.1 nM, respectively. A novel second-generation arginase inhibitor, arginase inhibitor 1 has demonstrated notable efficacy in models of myocardial ischemia/reperfusion injury (MI/RI). In both in vitro enzymatic and cellular assays for hARG I, arginase inhibitor 1 is highly effective. The IC50 value of arginase inhibitor 1 in CHO cells that overexpress hArgI is 8 μM. [1]
Arginase inhibitor 1 demonstrates potent activity in both enzymatic and cellular assays. In cell-free enzymatic assays, it inhibits human arginase I with an IC50 of 223 +/- 22.3 nM and human arginase II with an IC50 of 509 +/- 85.1 nM. In recombinant cellular assays using CHO cells overexpressing human arginase I (hArgI), the compound shows an IC50 value of approximately 8 microM. The compound is highly effective in vitro, with its potency being well-characterized across multiple assay platforms. These data confirm that arginase inhibitor 1 is a potent inhibitor of both arginase isoforms, with slightly higher potency against arginase I compared to arginase II, and that its activity translates from biochemical assays to cell-based systems. |
| ln Vivo |
Arginase Inhibitor 1 had a terminal elimination half-life (t1/2) of 3.3 hours, hydrogen distribution, and systemic clearance of 1.86 L/kg and 7.89 mL/min in chow-dwelling mice after intravenous treatment of 10 mg/kg. The oral bioavailability of arginase inhibitor 1 (10 mg/kg, po) is 28%, and its Cmax is 0.45 mg/L [1].
In vivo studies in mouse models have characterized the pharmacokinetic and pharmacodynamic properties of arginase inhibitor 1. Following intravenous administration at a dose of 10 mg/kg in chow-fed mice, the compound exhibited a terminal elimination half-life (t1/2) of 3.3 hours, a volume of distribution of 1.86 L/kg, and a systemic clearance of 7.89 mL/min. When administered orally at 10 mg/kg, the compound achieved an oral bioavailability of 28% and a maximum plasma concentration (Cmax) of 0.45 mg/L. More importantly, arginase inhibitor 1 has demonstrated significant efficacy in reducing infarct size in rat models of myocardial ischemia/reperfusion injury, supporting its potential as a therapeutic agent for cardiovascular indications. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays (cell-free) for arginase inhibitor 1 typically involve measuring the inhibition of recombinant human arginase I and II activity using a colorimetric or fluorometric detection method. The enzyme is incubated with varying concentrations of the test compound and a substrate such as L-arginine, and the production of urea is quantified. Urea reacts with a chromogenic reagent (e.g., alpha-isonitrosopropiophenone) to produce a colored product measured spectrophotometrically. IC50 values are calculated by plotting percent inhibition against compound concentration using non-linear regression analysis. Assays are performed in 96-well or 384-well plate format with appropriate positive controls (known arginase inhibitors) and vehicle controls. Each concentration is typically tested in duplicate or triplicate to ensure reproducibility, and results are expressed as mean IC50 +/- standard deviation.
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| Cell Assay |
In vitro cellular assays for arginase inhibitor 1 are performed using recombinant CHO cells that overexpress human arginase I (hArgI). Cells are cultured in appropriate medium and exposed to varying concentrations of the test compound for a defined incubation period. Following treatment, cells are lysed, and intracellular arginase activity is measured using a similar urea detection method as in the enzymatic assays. The cellular IC50 value is determined from the dose-response curve; for arginase inhibitor 1, the cellular IC50 in CHO-hArgI cells is approximately 8 microM. This cell-based assay confirms that the compound can penetrate cells and inhibit the target enzyme in a physiologically relevant cellular context. Cytotoxicity is typically assessed in parallel using standard viability assays (e.g., MTT or CellTiter-Glo) to ensure that observed inhibition is not due to nonspecific cell toxicity.
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| Animal Protocol |
In vivo animal studies for arginase inhibitor 1 have been conducted in both mouse and rat models. In pharmacokinetic studies, male chow-fed mice receive the compound via intravenous (10 mg/kg) or oral (10 mg/kg) administration, and blood samples are collected at multiple time points post-dose. Plasma concentrations are analyzed by LC-MS/MS, and pharmacokinetic parameters including half-life, clearance, volume of distribution, oral bioavailability, and Cmax are calculated. In efficacy studies, a rat model of myocardial ischemia/reperfusion injury is employed, where animals undergo temporary coronary artery occlusion followed by reperfusion. Arginase inhibitor 1 or vehicle is administered prior to reperfusion, and infarct size is measured by TTC staining as a percentage of the area at risk. The compound significantly reduces infarct size compared to vehicle controls, demonstrating cardioprotective efficacy.
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| ADME/Pharmacokinetics |
Arginase inhibitor 1 exhibits moderate oral bioavailability and a relatively short half-life in preclinical species. Following intravenous administration in mice at 10 mg/kg, the compound shows a terminal elimination half-life of 3.3 hours, a volume of distribution of 1.86 L/kg (indicating distribution into tissues), and a systemic clearance of 7.89 mL/min. After oral administration at the same dose, the compound achieves an oral bioavailability of 28%, with a maximum plasma concentration (Cmax) of 0.45 mg/L. The compound is soluble in DMSO, and fresh solutions are recommended due to instability of stock solutions. These pharmacokinetic properties suggest that while the compound has measurable oral exposure, its relatively low bioavailability and short half-life may necessitate multiple daily dosing or formulation optimization for therapeutic applications.
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| Toxicity/Toxicokinetics |
Toxicological data for arginase inhibitor 1 are limited as the compound is primarily used for research purposes. As a boron-containing compound, its toxicity profile would need to be carefully evaluated, as boron-containing drugs can have unique metabolic and elimination pathways. The compound is not approved for human use and is strictly intended for laboratory research only. Standard in vitro cytotoxicity assays in cell lines (such as CHO cells) are typically performed alongside efficacy studies to rule out nonspecific toxicity. For in vivo studies, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. However, comprehensive toxicological characterization including genotoxicity, cardiotoxicity, and repeated-dose toxicity studies has not been reported in the public domain. Any potential therapeutic development would require extensive safety evaluation in accordance with regulatory guidelines.
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| References | |
| Additional Infomation |
Arginase inhibitor 1 is a second-generation arginase inhibitor developed with improved potency and selectivity compared to earlier compounds. Its mechanism of action involves competitive inhibition of the arginase enzyme, preventing the conversion of L-arginine to urea and ornithine, thereby increasing substrate availability for nitric oxide synthase and enhancing nitric oxide production. The compound has been studied primarily for cardiovascular indications, particularly myocardial reperfusion injury. It is not currently in clinical trials and has not received regulatory approval for any therapeutic indication. The compound's boron-containing structure is characteristic of many arginase inhibitors, as the boronic acid moiety can form reversible covalent bonds with the active site manganese ions. Research has shown significant activity in rat models of ischemia/reperfusion injury, supporting further investigation. The compound is available from multiple research chemical suppliers for non-clinical research purposes only.
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| Molecular Formula |
C13H27BN2O4
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|---|---|
| Molecular Weight |
286.1755
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| Exact Mass |
286.206
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| CAS # |
1345808-25-4
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| PubChem CID |
66833213
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| Appearance |
White to gray solid powder
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| LogP |
0.925
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
20
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| Complexity |
298
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| Defined Atom Stereocenter Count |
1
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| SMILES |
B(CCCC[C@@](CCN1CCCCC1)(C(=O)O)N)(O)O
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| InChi Key |
CHPILBYRQPOXMV-CYBMUJFWSA-N
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| InChi Code |
InChI=1S/C13H27BN2O4/c15-13(12(17)18,6-2-3-8-14(19)20)7-11-16-9-4-1-5-10-16/h19-20H,1-11,15H2,(H,17,18)/t13-/m1/s1
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| Chemical Name |
(2R)-2-amino-6-borono-2-(2-piperidin-1-ylethyl)hexanoic 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 |
| 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) |
DMSO : ≥ 48 mg/mL (~167.73 mM)
H2O : ≥ 30 mg/mL (~104.83 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (5.84 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 16.7 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: ≥ 1.67 mg/mL (5.84 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 16.7 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: ≥ 1.67 mg/mL (5.84 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: 65 mg/mL (227.13 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 | 3.4943 mL | 17.4715 mL | 34.9430 mL | |
| 5 mM | 0.6989 mL | 3.4943 mL | 6.9886 mL | |
| 10 mM | 0.3494 mL | 1.7472 mL | 3.4943 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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