| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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Purity: ≥98%
Freselestat (also known as ONO-6818) is a novel, potent and selective inhibitor of Human Neutrophil Elastase (HNE). Freselestat reduces inflammatory mediators during simulated extracorporeal circulation. ONO-6818 significantly reduced interleukin 8 and C5b-9 production. ONO-6818 did not modulate changes of CD11b and L-selectin during recirculation.
| Targets |
Recirculating fresh heparinized (3.75 U/mL) human blood in a roller pump and membrane oxygenator for 120 minutes with or without 1.0 μM Freselestat (ONO-6818) allowed for the establishment of simulated extracorporeal circulation. The Freselestat group showed a significant decrease in neutrophil elastase levels. Freselestat dramatically lowers the synthesis of C5b-9 and interleukin-8. L-selectin and CD11b alterations during recycling are not modulated by frecelsestat [3].
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| ln Vitro |
Recirculating fresh heparinized (3.75 U/mL) human blood in a roller pump and membrane oxygenator for 120 minutes with or without 1.0 μM Freselestat (ONO-6818) allowed for the establishment of simulated extracorporeal circulation. The Freselestat group showed a significant decrease in neutrophil elastase levels. Freselestat dramatically lowers the synthesis of C5b-9 and interleukin-8. L-selectin and CD11b alterations during recycling are not modulated by frecelsestat [3].
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| ln Vivo |
Hemoglobin, neutrophil counts in bronchoalveolar lavage fluid, and pulmonary myeloperoxidase activity are all affected by HNE. Treatment with Freselestat (ONO-6818; 10-100 mg/kg; oral; daily; for 8 weeks) attenuates these dose-dependent increases. ONO-6818 decreases pulmonary bleeding and neutrophil buildup in the lungs to prevent HNE-induced acute lung damage [1].
In a rat model of HNE-induced acute lung injury, oral administration of freselestat (ONO-6818) at 10 mg/kg and 100 mg/kg (given 1 hour before intratracheal HNE) dose-dependently attenuated HNE-induced lung hemorrhage, as measured by a significant reduction in hemoglobin concentration in bronchoalveolar lavage fluid (BALF) collected 6 hours post-HNE. [1] In the same acute model, oral freselestat (ONO-6818) at 100 mg/kg significantly suppressed HNE-induced neutrophil accumulation in the lung. This was evidenced by a reduction in neutrophil counts in BALF and a decrease in lung tissue myeloperoxidase (MPO) activity. The 10 mg/kg dose showed a trend but was not statistically significant for some parameters. [1] In a rat model of HNE-induced chronic emphysema (assessed 8 weeks post-HNE), oral pretreatment with freselestat (ONO-6818) at 10 mg/kg and 100 mg/kg significantly and dose-dependently inhibited the development of emphysematous changes. This was demonstrated by prevention of HNE-induced increases in functional residual capacity (FRC), total lung capacity (TLC), static lung compliance (Cst), and mean linear intercept (Lm - a measure of airspace enlargement). [1] The high dose (100 mg/kg) effectively normalized lung volumes (FRC, TLC), compliance, and airspace size (Lm) to levels comparable to the control group. [1] |
| Animal Protocol |
Animal/Disease Models: Human neutrophil elastase (HNE)-induced male Wistar rats (228 g) [1]
Doses: 10 mg/kg, 100 mg/kg Route of Administration: oral; Route of Administration: oral. Routine; continued for 8 weeks Experimental Results: HNE-induced increases in pulmonary myeloperoxidase activity, hemoglobin, and neutrophil counts in bronchoalveolar lavage fluid were dose-dependently attenuated. For the HNE-induced lung injury and emphysema model, young male Wistar rats (228 ± 15 g) were used. [1] Human neutrophil elastase (HNE, 200 U) was administered intratracheally using a microsprayer device. [1] Freselestat (ONO-6818) was dissolved in 0.5% carboxymethyl-cellulose (CMC) solution at a volume of 5 ml/kg. [1] The drug was administered orally (per os) as a single dose, 1 hour before the intratracheal application of HNE. [1] Two dose levels were tested: 10 mg/kg (low dose) and 100 mg/kg (high dose). The control group received HNE plus the 0.5% CMC vehicle. [1] For acute phase assessment (lung hemorrhage, neutrophil accumulation), animals were sacrificed 6 hours after HNE administration. Bronchoalveolar lavage was performed to collect BALF for analysis of hemoglobin and neutrophil counts. Lung tissue was harvested to measure myeloperoxidase (MPO) activity. [1] For chronic phase assessment (emphysema development), a separate set of animals was sacrificed 8 weeks after HNE administration. Before sacrifice, pulmonary function tests (FRC, TLC, Cst) were performed on anesthetized rats using a whole-body plethysmograph. After sacrifice, lungs were fixed for histomorphometric analysis to determine the mean linear intercept (Lm). [1] |
| References | |
| Additional Infomation |
Drug Indication
It has been studied for the treatment of chronic obstructive pulmonary disease (COPD). Mechanism of Action ONO-6818 inhibits neutrophil elastase activity, reducing the production of interleukin-8 and the formation of complement membrane attack complex. Consequently, neutrophil elastase levels are reduced during extracorporeal circulation stimulation. Freselestat (study code ONO-6818) has the chemical name C23H28N6O4 and a molecular weight of 452.51. It is a low molecular weight, specific, reversible non-peptide neutrophil elastase inhibitor. [1] It is an orally effective inhibitor. [1] The compound itself has been reported to have no direct effect on the degradation of elastin or collagen (based on personal communications cited in the text). Its mechanism of reducing lung injury is thought to be the direct inhibition of neutrophil elastase. [1] This study confirmed that it can effectively prevent HNE-induced acute lung injury (hemorrhagic, inflammatory) and chronic emphysema changes (alveolar enlargement, loss of elastic recoil) in rats. [1] |
| Molecular Formula |
C23H28N6O4
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| Molecular Weight |
452.50600
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| Exact Mass |
452.217
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| CAS # |
208848-19-5
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| Related CAS # |
Freselestat quarterhydrate
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| PubChem CID |
216294
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| Appearance |
White to off-white solid powder
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| Density |
1.32g/cm3
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| Index of Refraction |
1.633
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| LogP |
3.168
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
33
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| Complexity |
825
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YSIHYROEMJSOAS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H28N6O4/c1-13(2)17(18(31)20-27-28-22(33-20)23(3,4)5)26-16(30)12-29-19(14-9-7-6-8-10-14)25-11-15(24)21(29)32/h6-11,13,17H,12,24H2,1-5H3,(H,26,30)
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| Chemical Name |
2-(5-amino-6-oxo-2-phenylpyrimidin-1(6H)-yl)-N-(1-(5-(tert-butyl)-1,3,4-oxadiazol-2-yl)-3-methyl-1-oxobutan-2-yl)acetamide
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| Synonyms |
ONO-6818; ONO6818; ONO 6818; ONO-PO 736; ONO-PO-736; ONO PO 736;
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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) |
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 | 2.2099 mL | 11.0495 mL | 22.0990 mL | |
| 5 mM | 0.4420 mL | 2.2099 mL | 4.4198 mL | |
| 10 mM | 0.2210 mL | 1.1049 mL | 2.2099 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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