MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 510254 | Name: Alvelestat (AZD9688)
Featured New

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Avelestat, also known as AZD9668 and MPH-966, is a novel, oral inhibitor of neutrophil elastase (NE), an enzyme implicated in the signs, symptoms, and disease progression in NE-driven respiratory diseases such as bronchiectasis and chronic obstructive pulmonary disease via its role in the inflammatory process, mucus overproduction, and lung tissue damage. In cell-based assays, AZD9668 inhibited plasma NE activity in zymosan-stimulated whole blood. AZD9668 has the potential to reduce lung inflammation and the associated structural and functional changes in human diseases.

Chemical Structure

Alvelestat (AZD9688)
Alvelestat (AZD9688)
CAS#848141-11-7 (free base)

Theoretical Analysis

MedKoo Cat#: 510254

Name: Alvelestat (AZD9688)

CAS#: 848141-11-7 (free base)

Chemical Formula: C25H22F3N5O4S

Exact Mass: 545.1345

Molecular Weight: 545.53

Elemental Analysis: C, 55.04; H, 4.06; F, 10.45; N, 12.84; O, 11.73; S, 5.88

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
50mg USD 250.00 Ready to ship
100mg USD 450.00 Ready to ship
200mg USD 750.00 Ready to ship
500mg USD 1,650.00 Ready to ship
1g USD 2,950.00 Ready to ship
2g USD 5,250.00 Ready to ship
Show More
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
1240425-05-1 (tosylate) 848141-11-7 (free base) 1240425-11-9 (HCl)
Synonym
AZD9668; AZD 9668; AZD-9668; MPH966; MPH 966; MPH-966; Alvelestat;
IUPAC/Chemical Name
6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-N-((5-(methylsulfonyl)pyridin-2-yl)methyl)-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide
InChi Key
QNQZWEGMKJBHEM-UHFFFAOYSA-N
InChi Code
InChI=1S/C25H22F3N5O4S/c1-15-20(22-9-10-31-32(22)2)12-21(23(34)30-13-17-7-8-19(14-29-17)38(3,36)37)24(35)33(15)18-6-4-5-16(11-18)25(26,27)28/h4-12,14H,13H2,1-3H3,(H,30,34)
SMILES Code
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
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
Alvelestat (AZD9668) is an affinity and selective inhibitor of neutrophil elastase (NE) with a pIC50 value of 7.9 nM, a Ki value of 9.4 nM and a Kd value of 9.5 nM.
In vitro activity:
As NE is a major component of NETs (neutrophil extracellular traps), this study further examined whether alvelestat-mediated protection was also dependent on inhibition of NE activity in NETs. To address this issue, this study first stimulated adenocarcinoma human alveolar epithelial cells (A549) and human bronchial epithelial cells (HBE) with exogenous human-derived NETs and observed that administration of NETs enhanced cell death in A549 cells, while NETs barely caused mild damage in HBE cells as shown by PI staining and flow cytometry analysis (Figure 6A). However, NETs could induce an inflammatory response in both A549 cells and HBE cells (Figure 6B), confirming that NETs possess direct cytotoxic effects and induce inflammation. Co-incubation of exogenous NETs with alvelestat, anti-NE antibody and DNase I decreased cytotoxicity and inflammatory responses, as demonstrated by the significantly alleviated cell death and reduced inflammatory cytokine levels in the supernatant of the culture medium. These results confirmed that cytoprotection and inflammatory responses are mediated by targeting NETs and their components, such as NE. Reference: Oncotarget. 2018 Jan 5; 9(2): 1772–1784. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788598/
In vivo activity:
MPO is widely used as an inflammatory marker in FUIIM (5-FU induced intestinal mucositis) model. In addition, neutrophil infiltration and degranulation are mediated by NE and proteinase 3 (Pr3) release and cause tissue damage. The effects of MPH-966 treatment on FUIIM were studied using mice jejunums that were collected and homogenized. MPH-966’s ability to confer protective effects was determined by analyzing MPO, NE, and Pr3 activity. The results showed that MPH-966 significantly attenuated 5-FU-induced MPO, NE, and Pr3 activity in a dose-dependent manner (Fig. 2A–C). MPH-966’s ability to decrease NE expression in mice jejunums was further confirmed using IHC staining (Fig. 2D). This study is the first report to demonstrate the involvement of NE and Pr3 in FUIIM. It further supports a role for MPH-966 in modulating NE homeostasis and preventing FUIIM. Reference: Biomed Pharmacother. 2021 Feb;134:111152. https://pubmed.ncbi.nlm.nih.gov/33373916/
Solvent mg/mL mM
Solubility
DMSO 46.0 84.32
DMSO:PBS (pH 7.2) (1:5) 0.2 0.29
DMF 5.0 9.17
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 545.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Li H, Zhou X, Tan H, Hu Y, Zhang L, Liu S, Dai M, Li Y, Li Q, Mao Z, Pan P, Su X, Hu C. Neutrophil extracellular traps contribute to the pathogenesis of acid-aspiration-induced ALI/ARDS. Oncotarget. 2017 Nov 28;9(2):1772-1784. doi: 10.18632/oncotarget.22744. PMID: 29416730; PMCID: PMC5788598. 2. Chen KJ, Chen YL, Ueng SH, Hwang TL, Kuo LM, Hsieh PW. Neutrophil elastase inhibitor (MPH-966) improves intestinal mucosal damage and gut microbiota in a mouse model of 5-fluorouracil-induced intestinal mucositis. Biomed Pharmacother. 2021 Feb;134:111152. doi: 10.1016/j.biopha.2020.111152. Epub 2020 Dec 26. PMID: 33373916. 3. Delbosc S, Rouer M, Alsac JM, Louedec L, Philippe M, Meilhac O, Whatling C, Michel JB. Elastase inhibitor AZD9668 treatment prevented progression of experimental abdominal aortic aneurysms. J Vasc Surg. 2016 Feb;63(2):486-92.e1. doi: 10.1016/j.jvs.2014.07.102. Epub 2014 Aug 28. PMID: 25175632. 4. Stevens T, Ekholm K, Gränse M, Lindahl M, Kozma V, Jungar C, Ottosson T, Falk-Håkansson H, Churg A, Wright JL, Lal H, Sanfridson A. AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J Pharmacol Exp Ther. 2011 Oct;339(1):313-20. doi: 10.1124/jpet.111.182139. Epub 2011 Jul 26. PMID: 21791628.
In vitro protocol:
1. Li H, Zhou X, Tan H, Hu Y, Zhang L, Liu S, Dai M, Li Y, Li Q, Mao Z, Pan P, Su X, Hu C. Neutrophil extracellular traps contribute to the pathogenesis of acid-aspiration-induced ALI/ARDS. Oncotarget. 2017 Nov 28;9(2):1772-1784. doi: 10.18632/oncotarget.22744. PMID: 29416730; PMCID: PMC5788598. 2. Stevens T, Ekholm K, Gränse M, Lindahl M, Kozma V, Jungar C, Ottosson T, Falk-Håkansson H, Churg A, Wright JL, Lal H, Sanfridson A. AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J Pharmacol Exp Ther. 2011 Oct;339(1):313-20. doi: 10.1124/jpet.111.182139. Epub 2011 Jul 26. PMID: 21791628.
In vivo protocol:
1. Chen KJ, Chen YL, Ueng SH, Hwang TL, Kuo LM, Hsieh PW. Neutrophil elastase inhibitor (MPH-966) improves intestinal mucosal damage and gut microbiota in a mouse model of 5-fluorouracil-induced intestinal mucositis. Biomed Pharmacother. 2021 Feb;134:111152. doi: 10.1016/j.biopha.2020.111152. Epub 2020 Dec 26. PMID: 33373916. 2. Delbosc S, Rouer M, Alsac JM, Louedec L, Philippe M, Meilhac O, Whatling C, Michel JB. Elastase inhibitor AZD9668 treatment prevented progression of experimental abdominal aortic aneurysms. J Vasc Surg. 2016 Feb;63(2):486-92.e1. doi: 10.1016/j.jvs.2014.07.102. Epub 2014 Aug 28. PMID: 25175632.
1: Lulla AR, Akli S, Karakas C, Caruso JA, Warma LD, Fowlkes NW, Rao X, Wang J, Hunt KK, Watowich SS, Keyomarsi K. Neutrophil elastase remodels mammary tumors to facilitate lung metastasis. Mol Cancer Ther. 2023 Oct 5. doi: 10.1158/1535-7163.MCT-23-0414. Epub ahead of print. PMID: 37796181. 2: Bhagat A, Shrestha P, Jeyabal P, Peng Z, Watowich SS, Kleinerman ES. Doxorubicin-induced cardiotoxicity is mediated by neutrophils through release of neutrophil elastase. Front Oncol. 2022 Aug 10;12:947604. doi: 10.3389/fonc.2022.947604. PMID: 36033503; PMCID: PMC9400062. 3: Sengupta S, Reddy JR, Rajesh N, Jaiswal A, Mabalirajan U, Palakodety RK, Mukherjee P, Bandyopadhyay A. Novel benzoxazinone derivative as potent human neutrophil elastase inhibitor: Potential implications in lung injury. Eur J Pharmacol. 2022 Sep 15;931:175187. doi: 10.1016/j.ejphar.2022.175187. Epub 2022 Aug 8. PMID: 35952844. 4: Otsuka R, Miyagi-Shiohira C, Kuwae K, Nishime K, Tamaki Y, Yonaha T, Sakai- Yonaha M, Yamasaki I, Shinzato M, Saitoh I, Watanabe M, Noguchi H. Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation. J Clin Med. 2022 Jul 23;11(15):4290. doi: 10.3390/jcm11154290. PMID: 35893379; PMCID: PMC9330829. 5: Garciafigueroa Y, Phillips BE, Engman C, Trucco M, Giannoukakis N. Neutrophil-Associated Inflammatory Changes in the Pre-Diabetic Pancreas of Early-Age NOD Mice. Front Endocrinol (Lausanne). 2021 Mar 10;12:565981. doi: 10.3389/fendo.2021.565981. PMID: 33776903; PMCID: PMC7988208. 6: Bi Y, Zhong H, Xu K, Wu G, Han X. Regarding "Elastase inhibitor AZD9668 treatment prevented progression of experimental abdominal aortic aneurysms". J Vasc Surg. 2015 Nov;62(5):1386. doi: 10.1016/j.jvs.2015.02.056. PMID: 26506280. 7: Nordenmark LH, Taylor R, Jorup C. Feasibility of Computed Tomography in a Multicenter COPD Trial: A Study of the Effect of AZD9668 on Structural Airway Changes. Adv Ther. 2015 Jun;32(6):548-66. doi: 10.1007/s12325-015-0215-3. Epub 2015 Jun 5. PMID: 26043724. 8: Delbosc S, Rouer M, Alsac JM, Louedec L, Philippe M, Meilhac O, Whatling C, Michel JB. Elastase inhibitor AZD9668 treatment prevented progression of experimental abdominal aortic aneurysms. J Vasc Surg. 2016 Feb;63(2):486-92.e1. doi: 10.1016/j.jvs.2014.07.102. Epub 2014 Aug 28. PMID: 25175632. 9: Leidy NK, Murray LT, Jones P, Sethi S. Performance of the EXAcerbations of chronic pulmonary disease tool patient-reported outcome measure in three clinical trials of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014 Mar;11(3):316-25. doi: 10.1513/AnnalsATS.201309-305OC. PMID: 24432712. 10: Henriksen PA. The potential of neutrophil elastase inhibitors as anti- inflammatory therapies. Curr Opin Hematol. 2014 Jan;21(1):23-8. doi: 10.1097/MOH.0000000000000001. PMID: 24241342. 11: Stockley R, De Soyza A, Gunawardena K, Perrett J, Forsman-Semb K, Entwistle N, Snell N. Phase II study of a neutrophil elastase inhibitor (AZD9668) in patients with bronchiectasis. Respir Med. 2013 Apr;107(4):524-33. doi: 10.1016/j.rmed.2012.12.009. Epub 2013 Feb 20. PMID: 23433769. 12: Gunawardena KA, Gullstrand H, Perrett J. Pharmacokinetics and safety of AZD9668, an oral neutrophil elastase inhibitor, in healthy volunteers and patients with COPD. Int J Clin Pharmacol Ther. 2013 Apr;51(4):288-304. doi: 10.5414/CP201674. PMID: 23391369. 13: Vogelmeier C, Aquino TO, O'Brien CD, Perrett J, Gunawardena KA. 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. doi: 10.3109/15412555.2011.641803. PMID: 22458939. 14: Sjö P. Neutrophil elastase inhibitors: recent advances in the development of mechanism-based and nonelectrophilic inhibitors. Future Med Chem. 2012 Apr;4(5):651-60. doi: 10.4155/fmc.12.17. PMID: 22458683. 15: Elborn JS, Perrett J, Forsman-Semb K, Marks-Konczalik J, Gunawardena K, Entwistle N. Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis. Eur Respir J. 2012 Oct;40(4):969-76. doi: 10.1183/09031936.00194611. Epub 2012 Jan 20. PMID: 22267768. 16: Kuna P, Jenkins M, O'Brien CD, Fahy WA. AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD. Respir Med. 2012 Apr;106(4):531-9. doi: 10.1016/j.rmed.2011.10.020. Epub 2011 Dec 23. PMID: 22197578. 17: Stevens T, Ekholm K, Gränse M, Lindahl M, Kozma V, Jungar C, Ottosson T, Falk-Håkansson H, Churg A, Wright JL, Lal H, Sanfridson A. AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J Pharmacol Exp Ther. 2011 Oct;339(1):313-20. doi: 10.1124/jpet.111.182139. Epub 2011 Jul 26. PMID: 21791628. 18: Norman P. Crystalline form of a neutrophil elastase inhibitor, 6-methyl-5-(1 -methyl-1H-pyrazol-5-yl)-N-{[5-(methylsulfonyl)pyridin-2-yl]methyl}-2-oxo-1-[3-( trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide p-toluene sulfonate - is it AZD-9668?: WO-2010094964. Expert Opin Ther Pat. 2011 Feb;21(2):277-80. doi: 10.1517/13543776.2011.535813. Epub 2011 Jan 11. PMID: 21222548. 19: Seale JP. European Respiratory Society (ERS) - 20th Annual Congress. IDrugs. 2010 Nov;13(11):762-4. PMID: 21046521.

View History

Hycanthone free base

Hycanthone free base

(E)-4-Undecenal

(E)-4-Undecenal

VU0431316

VU0431316

VU0415371

VU0415371

ZL0513

ZL0513