Alvelestat
Based on 11 publication(s) in Google Scholar
Alvelestat (AZD9668) is an orally active, selective inhibitor of neutrophil elastase. Alvelestat reduces elastase activity, myeloperoxidase release, neutrophil recruitment and activation, and calcium phosphate precipitation; promotes smooth muscle cell colonization and collagen deposition; and inhibits the formation of neutrophil extracellular traps (NETs) as well as NET-derived neutrophil elastase activity. Alvelestat restores endothelial dysfunction, regulates antioxidant factors, improves the expression of endothelial tight junctions, reduces vascular leakage, and accelerates wound healing. Alvelestat prevents pulmonary hemorrhage, matrix protein degradation, airspace enlargement, and small airway wall remodeling; and alleviates cigarette-induced inflammatory responses. Alvelestat inhibits the growth of abdominal aortic aneurysms exacerbated by Porphyromonas gingivalis. Alvelestat can be used in research related to chronic obstructive pulmonary disease, abdominal aortic aneurysm, radiation-induced skin injury, and bronchiectasis.
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- Purity: 99.87%
- CAS No.: 848141-11-7
- 화학식: C25H22F3N5O4S
- 분자량:545.53
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Publications Citing Use of MedChemExpress (MCE) Alvelestat
More- Cancer Cell. 2021 Mar 8;39(3):423-437.e7. [Abstract]
- Cell Death Dis. 2025 Apr 8;16(1):264. [Abstract]
- J Immunother Cancer. 2025 Feb 26;13(2):e010813. [Abstract]
- Neural Regen Res. 2023 Oct;18(10):2252-2259. [Abstract]
- NPJ Regen Med. 2020 Oct 30;5(1):19. [Abstract]
- Int J Mol Sci. 2024 Dec 27;26(1):143. [Abstract]
- Int Immunopharmacol. 2024 Nov 5;143(Pt 3):113534. [Abstract]
- FEBS Open Bio. 2018 Mar 25;8(5):751-763. [Abstract]
- bioRxiv. 2025 February 28.
- bioRxiv. 2023 Nov 13.
- Biomed Pharmacother. 2021 Feb:134:111152. [Abstract]
Biological Activity
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MMP-9 |
IL-6 |
Claudin-5 |
IL-1β |
Alvelestat potently, fully reversibly and selectively inhibits human neutrophil elastase, with at least 100-fold selectivity over other serine proteases, enzymes, receptors and ion channels[1].
Alvelestat (AZD9668) potently inhibits purified rat neutrophil elastase with an IC50 of approximately 7 nM; it also potently inhibits purified human neutrophil elastase with an IC50 of approximately 8 nM[2].
Alvelestat (AZD9668) (20 μg/mL; 3 h) potently inhibits NE activity and NET formation in human polymorphonuclear neutrophils (PMNs) stimulated by IR + PMA; it also potently inhibits neutrophil elastase (NE) activity in isolated human neutrophil extracellular traps (NETs)[3].
Alvelestat binds to purified human neutrophil elastase with high affinity in a rapid and reversible manner (KD = 9.5 nM), potently inhibits purified human neutrophil elastase (pIC50 = 7.9, IC50 = 12 nM), shows high selectivity over other serine proteases, and exhibits favorable cross-species activity against neutrophil elastase derived from mice, rats, guinea pigs, and dogs[4].
Alvelestat potently inhibits neutrophil elastase activity in zymosan-stimulated human whole blood (pIC50 = 7.36, IC50 = 44 nM); it also potently inhibits cell-associated neutrophil elastase activity in human polymorphonuclear cells stimulated by LPS and fMLP (pIC50 = 7.31, IC50 = 48 nM)[4].
Alvelestat potently inhibits the activity of neutrophil elastase released in a burst from Cytochalasin B (HY-16928)-pretreated, fMLP-stimulated human polymorphonuclear cells (pIC50 = 7.30, IC50 = 50 nM)[4].
Alvelestat (20 μg/mL; 24 h) improves the angiogenic functions (branch point formation and tube length) of HUVECs treated with IR + NET; it restores the endothelial barrier function of IR + NET-treated HUVECs and the expression of tight junction proteins claudin-5 and occludin in HUVECs, and upregulates the expression of antioxidant factors NRF2 and HO-1[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:irradiated HUVECs treated with NETs
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Concentration:20 μg/mL
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Incubation Time:24 h
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Result:Significantly increased the relative band intensities of tight junction proteins claudin-5 and occludin in IR + NET-treated HUVECs compared to untreated IR + NET controls.
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Cell Line:irradiated HUVECs treated with NETs
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Concentration:20 μg/mL
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Incubation Time:24 h
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Result:Significantly increased the relative mRNA levels of antioxidative factors NRF2 and HO-1 in IR + NET-treated HUVECs compared to untreated IR + NET controls.
Alvelestat (0.1-5 mg/kg; p.o.) significantly attenuates pulmonary hemorrhage induced by human neutrophil elastase (NE) in female C57BL/6JBomTac mice[4].
Alvelestat (2.5-20 mg/kg; p.o.) significantly reduces collagen degradation induced by human neutrophil elastase (NE) in female HanTac: WH rats; at doses of 10 mg/kg and above, it reduces elastin degradation[4].
Alvelestat (1-10 mg/kg; p.o.; twice daily for 4 consecutive days) reduces smoke-induced BAL neutrophil counts in female BALB/cJBomTac mice, and decreases IL-1β levels in BAL at doses ≥1 mg/kg[4].
Alvelestat (100 mg/kg; p.o.; once daily) completely inhibits smoke-induced pulmonary inflammation, emphysema and small airway remodeling in female Hartley guinea pigs[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SKH-1 (male, 6-8 weeks old, radiation-induced skin injury model)[3]
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Dosage:10 mg/kg
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Administration:p.o.; daily; from day of irradiation until euthanasia
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Result:Lowered Evans blue leakage fold change from 1.57 to 1.30 versus non-irradiated groups.
Restored colocalization of tight junction proteins claudin-5 and occludin on CD31+ vasculature.
Dampened NET deposition marked by CitH3 immunostaining signals.
Shrank wound area evidently at 2, 3 and 4 weeks post radiation.
Mitigated TEWL and improved skin hydration across 2-4 weeks post exposure.
Cut skin injury histological scores from 8.8 down to 6.6.
Suppressed type I collagen mRNA abundance markedly.
Lessened Ly6G+ and MPO+ neutrophil infiltration proportions.
Dropped IL-6 and Mmp-9 transcript levels relative to irradiated counterparts.
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Animal Model:C57BL/6JBomTac (female, 18-20 g, intratracheal administration of human NE)[4]
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Dosage:0.1 mg/kg; 0.5 mg/kg; 1 mg/kg; 1.5 mg/kg; 2 mg/kg; 2.5 mg/kg; 3.5 mg/kg; 5 mg/kg
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Administration:p.o.
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Result:Suppressed BAL hemoglobin elevation triggered by human NE at dosages above 1.5 mg/kg.
Achieved robust suppression at 1.5, 2, 2.5, 3.5 and 5 mg/kg versus NE-only cohorts.
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Animal Model:HanTac: WH (female, 180-220 g, intratracheal administration of human NE)[4]
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Dosage:2.5 mg/kg; 5 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:p.o.
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Result:Significantly inhibited NE-induced increases in BAL hydroxyproline in a dose-dependent manner at doses ≥2.5 mg/kg.
Significantly inhibited NE-induced increases in BAL desmosine at doses of 10 mg/kg and 20 mg/kg.
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Animal Model:BALB/cJBomTac (female, 18-20 g, whole-body exposure to cigarette smoke)[4]
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Dosage:1 mg/kg; 3 mg/kg; 6 mg/kg; 10 mg/kg
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Administration:p.o.; twice daily; 4 days
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Result:Significantly reduced BAL neutrophil counts at doses ≥6 mg/kg.
Significantly reduced BAL IL-1β levels relative to smoke-exposed controls at doses ≥1 mg/kg.
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Animal Model:Hartley (female, initial weight ~350 g, nose-only exposure to tobacco smoke for 24 weeks)[4]
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Dosage:100 mg/kg (prophylactic); 100 mg/kg (therapeutic)
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Administration:p.o.; once daily; 24 weeks (prophylactic); once daily; 12 weeks (therapeutic)
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Result:Blocked smoke-triggered BAL neutrophil and macrophage elevation under prophylactic and therapeutic regimens.
Eliminated smoke-mediated pulmonary emphysema in two administration modes.
Abolished smoke-caused small airway remodeling via preventive and therapeutic dosing.
Chemical Information
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CAS No. 848141-11-7
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Appearance Solid
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분자량 545.53
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화학식 C25H22F3N5O4S
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Color White to light yellow
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SMILES
O=C(C1=CC(C2=CC=NN2C)=C(C)N(C3=CC=CC(C(F)(F)F)=C3)C1=O)NCC4=NC=C(S(=O)(C)=O)C=C4
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Synonyms
AZD9668
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (11)
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Journal Impact Factor
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Most Recent
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Cancer Cell
Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. [Abstract]2021 Mar 8;39(3):423-437.e7. PMID: 33450198 -
Cell Death Dis
Downregulation of tropomyosin 2 promotes the progression of lung adenocarcinoma by regulating neutrophil infiltration through neutrophil elastase. [Abstract]2025 Apr 8;16(1):264. PMID: 40199876 -
J Immunother Cancer
Neutrophil extracellular traps impede cancer metastatic seeding via protease-activated receptor 2-mediated downregulation of phagocytic checkpoint CD24. [Abstract]2025 Feb 26;13(2):e010813. PMID: 40010762 -
Neural Regen Res
2023 Oct;18(10):2252-2259. PMID: 37056145 -
NPJ Regen Med
2020 Oct 30;5(1):19. PMID: 33298919 -
Int J Mol Sci
Neutrophil Extracellular Trap Formation Model Induced by Monosodium Urate and Phorbol Myristate Acetate: Involvement in MAPK Signaling Pathways. [Abstract]2024 Dec 27;26(1):143. PMID: 39796001 -
Int Immunopharmacol
HSYA ameliorates venous thromboembolism by depleting the formation of TLR4/NF-κB pathway-dependent neutrophil extracellular traps. [Abstract]2024 Nov 5;143(Pt 3):113534. PMID: 39504860 -
FEBS Open Bio
Identification of small-molecule elastase inhibitors as antagonists of IL-36 cytokine activation. [Abstract]2018 Mar 25;8(5):751-763. PMID: 29744290 -
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Biomed Pharmacother
Neutrophil elastase inhibitor (MPH-966) improves intestinal mucosal damage and gut microbiota in a mouse model of 5-fluorouracil-induced intestinal mucositis. [Abstract]2021 Feb:134:111152. PMID: 33373916
용액&용해도
DMSO : ≥ 33 mg/mL (60.49 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.58 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.58 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
순도&문서
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Data Sheet (286 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Vogelmeier C, et al. A randomised, placebo-controlled, dose-finding study of AZD9668, an oral inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary disease treated with tiotropium. COPD. 2012 Apr;9(2):111-20. [Content Brief]
[2]. Delbosc S, et al. Elastase inhibitor AZD9668 treatment prevented progression of experimental abdominal aortic aneurysms. Journal of vascular surgery. 2016 Feb;63(2):486-92.e1. [Content Brief]
[3]. Park JH, et al. AZD 9668, a neutrophil elastase inhibitor, promotes wound healing in the irradiated skin by inhibiting NET-derived vascular dysfunction. International immunopharmacology. 2025 Jun 26;159:114860. [Content Brief]
[4]. Stevens T, et al. AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase. The Journal of pharmacology and experimental therapeutics. 2011 Oct;339(1):313-20. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.8331 mL | 9.1654 mL | 18.3308 mL | 45.8270 mL |
| 5 mM | 0.3666 mL | 1.8331 mL | 3.6662 mL | 9.1654 mL | |
| 10 mM | 0.1833 mL | 0.9165 mL | 1.8331 mL | 4.5827 mL | |
| 15 mM | 0.1222 mL | 0.6110 mL | 1.2221 mL | 3.0551 mL | |
| 20 mM | 0.0917 mL | 0.4583 mL | 0.9165 mL | 2.2913 mL | |
| 25 mM | 0.0733 mL | 0.3666 mL | 0.7332 mL | 1.8331 mL | |
| 30 mM | 0.0611 mL | 0.3055 mL | 0.6110 mL | 1.5276 mL | |
| 40 mM | 0.0458 mL | 0.2291 mL | 0.4583 mL | 1.1457 mL | |
| 50 mM | 0.0367 mL | 0.1833 mL | 0.3666 mL | 0.9165 mL | |
| 60 mM | 0.0306 mL | 0.1528 mL | 0.3055 mL | 0.7638 mL |
Alvelestat Related Classifications
HY-15651 Related Classifications
Powered by Bioz
- Alvelestat
- 848141-11-7
- AZD9668
- AZD 9668
- AZD-9668
- Elastase
- Claudin
- Interleukin Related
- MMP
- abdominal aortic aneurysm
- human polymorphonuclear cells
- chronic obstructive pulmonary disease
- HUVECs
- radiation-induced skin injury
- NET formation
- neutrophil elastase
- Porphyromonas gingivalis
- bronchiectasis
- myeloperoxidase
- Inhibitor
- inhibitor
- inhibit