1. Metabolic Enzyme/Protease
  2. Elastase

Alvelestat (Synonyms: AZD9668)

Cat. No.: HY-15651
Handling Instructions

Alvelestat (AZD9668) is a novel, oral inhibitor of neutrophil elastase (NE) with the pIC50 of 7.9 for Human NE.

For research use only. We do not sell to patients.
Alvelestat Chemical Structure

Alvelestat Chemical Structure

CAS No. : 848141-11-7

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10 mM * 1 mL in DMSO $156 In-stock
5 mg $130 In-stock
10 mg $210 In-stock
50 mg $750 In-stock
100 mg $1250 In-stock
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500 mg   Get quote  

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Description

Alvelestat (AZD9668) is a novel, oral inhibitor of neutrophil elastase (NE) with the pIC50 of 7.9 for Human NE. IC50 Value: 7.9 ± 0.12 (pIC50, Human NE); 4.9 nM (Ki value, Human NE) [1] Target: Neutrophil elastase in vitro: AZD9668 had a high binding affinity for human NE (KD = 9.5 nM) and potently inhibited NE activity. The calculated pIC50 (IC50) and Ki values for AZD9668 for human NE were 7.9 (12 nM) and 4.9 nM, respectively. In contrast to earlier NE inhibitors, the interaction between AZD9668 and NE was rapidly reversible. AZD9668 was also highly selective for NE over other neutrophil-derived serine proteases. In cell-based assays, AZD9668 inhibited plasma NE activity in zymosan-stimulated whole blood. In isolated human polymorphonuclear cells, AZD9668 inhibited NE activity on the surface of stimulated cells and in the supernatant of primed, stimulated cells.AZD9668 showed good crossover potency to NE from other species [1]. in vivo: Six hundred and fifteen patients were randomised: placebo (302), AZD9668 60 mg bid (313). AZD9668 showed no effect on lung function: change in mean pre-bronchodilator FEV1 versus placebo was 0.01L (95% confidence interval: -0.03, 0.05; p=0.533). AZD9668 did not significantly improve respiratory signs and symptoms, SGRQ-C score or time to first exacerbation. Adverse events were similar for AZD9668 and placebo [2]. AZD9668 was well tolerated at single doses up to 150 mg and multiple doses up to 70 mg twice daily. PK were dose linear; median time to peak plasma concentration was reached at 0.5 - 1.5 hours and the short elimination half-life was consistent with twice daily dosing. Steady state was reached by Day 2 of twice daily dosing with negligible accumulation. Approximately 40% of AZD9668 was eliminated renally as unchanged compound. Ex vivo zymosan-stimulated inhibition of NE activity was dose-dependent, with maximal inhibition achieved at 60 mg [4]. Toxicity: A total of 838 patients were randomised to AZD9668 5 mg bid (212 patients), 20 mg bid (206 patients), 60 mg bid (202 patients) or placebo (218 patients). AZD9668 showed no effect on lung function, respiratory signs and symptoms, QoL or biomarkers [3]. Clinical trial: Phase II study of a neutrophil elastase inhibitor (AZD9668) in patients with bronchiectasis.

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT01161355 AstraZeneca Healthy June 2010 Phase 1
NCT01035411 AstraZeneca Chronic Obstructive Pulmonary Disease November 2009 Phase 1
NCT01034982 AstraZeneca Chronic Obstructive Pulmonary Disease November 2009 Phase 1
NCT01147549 AstraZeneca Healthy June 2010 Phase 1
NCT02669251 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Chronic Graft vs Host Disease|Chronic Graft-Versus-Host-Disease|Bronchiolitis Obliterans Syndrome January 20, 2016 Phase 1|Phase 2
NCT00757848 AstraZeneca Cystic Fibrosis October 2008 Phase 2
NCT01214122 AstraZeneca Pharmacokinetics|Pharmacodynamics November 2010 Phase 1
NCT00769119 AstraZeneca Bronchiectasis September 2008 Phase 2
NCT00703391 AstraZeneca Chronic Obstructive Pulmonary Disease (COPD) June 2008 Phase 2
NCT01023516 AstraZeneca Chronic Obstructive Pulmonary Disease (COPD) November 2009 Phase 2
NCT00949975 AstraZeneca Chronic Obstructive Pulmonary Disease July 2009 Phase 2
NCT01054170 AstraZeneca Chronic Obstructive Pulmonary Disease (COPD) January 2010 Phase 2
NCT02597101 Nick Giannoukakis, PhD|National Institutes of Health (NIH)|University of Pittsburgh|University of South Florida|AstraZeneca|Allegheny Singer Research Institute Type 2 Diabetes Mellitus|Insulin Resistance November 2015 Phase 2
NCT01161355 AstraZeneca Healthy June 2010 Phase 1
NCT01035411 AstraZeneca Chronic Obstructive Pulmonary Disease November 2009 Phase 1
NCT01034982 AstraZeneca Chronic Obstructive Pulmonary Disease November 2009 Phase 1
NCT01147549 AstraZeneca Healthy June 2010 Phase 1
NCT02669251 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Chronic Graft vs Host Disease|Chronic Graft-Versus-Host-Disease|Bronchiolitis Obliterans Syndrome January 20, 2016 Phase 1|Phase 2
NCT00757848 AstraZeneca Cystic Fibrosis October 2008 Phase 2
NCT01214122 AstraZeneca Pharmacokinetics|Pharmacodynamics November 2010 Phase 1
NCT00769119 AstraZeneca Bronchiectasis September 2008 Phase 2
NCT00703391 AstraZeneca Chronic Obstructive Pulmonary Disease (COPD) June 2008 Phase 2
NCT01023516 AstraZeneca Chronic Obstructive Pulmonary Disease (COPD) November 2009 Phase 2
NCT00949975 AstraZeneca Chronic Obstructive Pulmonary Disease July 2009 Phase 2
NCT01054170 AstraZeneca Chronic Obstructive Pulmonary Disease (COPD) January 2010 Phase 2
NCT02597101 Nick Giannoukakis, PhD|National Institutes of Health (NIH)|University of Pittsburgh|University of South Florida|AstraZeneca|Allegheny Singer Research Institute Type 2 Diabetes Mellitus|Insulin Resistance November 2015 Phase 2
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References
Molecular Weight

545.53

Formula

C₂₅H₂₂F₃N₅O₄S

CAS No.

848141-11-7

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 33 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Alvelestat
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