Alvelestat (AZD9668)

Catalog No.S7218 Synonyms: Avelestat

Alvelestat (AZD9668) Chemical Structure

Molecular Weight(MW): 545.53

Alvelestat (AZD9668) is an oral, highly selective inhibitor of neutrophil elastase (NE) with IC50 and Ki of 12 nM and 9.4 nM, at least 600-fold more selective over other serine proteases. Phase 2.

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Choose Selective Serine Protease Inhibitors

Biological Activity

Description Alvelestat (AZD9668) is an oral, highly selective inhibitor of neutrophil elastase (NE) with IC50 and Ki of 12 nM and 9.4 nM, at least 600-fold more selective over other serine proteases. Phase 2.
Targets
neutrophil elastase [1]
(Cell-free assay)
neutrophil elastase [1]
(Cell-free assay)
9.4 nM(Ki) 12 nM
In vitro

AZD9668 inhibits plasma NE activity in zymosan-stimulated whole blood, and also inhibits NE activity on the surface of stimulated polymorphonuclear cells and in the supernatant of primed, stimulated cells. [1]

In vivo In mice and rats, AZD9668 (p.o.) prevents human NE-induced lung injury. In a mouse model of smoke-induced airway inflammation, AZD9668 significantly reduces the number of BAL neutrophils and BAL IL-1β. In a guinea pig chronic smoke model, AZD9668 prevents airspace enlargement and small airway wall remodeling in guinea pigs in response to chronic tobacco smoke exposure. [1]

Protocol

Animal Research:

[1]

+ Expand
  • Animal Models: Human NE-induced acute lung injury in mice or rats, guinea pig chronic smoke model.
  • Formulation: 0.5% hydroxypropyl methylcellulose in citrate buffer, 20% glucose and 0.1% polysorbate in water or corn oil
  • Dosages: ~10 mg/kg (mice); ~20 mg/kg (rats); ~100 mg/kg (pigs)
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (183.3 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 545.53
Formula

C25H22F3N5O4S

CAS No. 848141-11-7
Storage powder
in solvent
Synonyms Avelestat

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02669251 Recruiting Chronic Graft vs Host Disease|Chronic Graft-Versus-Host-Disease|Bronchiolitis Obliterans Syndrome National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) April 28 2016 Phase 1|Phase 2
NCT02597101 Active not recruiting Type 2 Diabetes Mellitus|Insulin Resistance Nick Giannoukakis PhD|National Institutes of Health (NIH)|University of Pittsburgh|University of South Florida|AstraZeneca|Allegheny Singer Research Institute November 2015 Phase 2
NCT01214122 Withdrawn Pharmacokinetics|Pharmacodynamics AstraZeneca November 2010 Phase 1
NCT01161355 Completed Healthy AstraZeneca June 2010 Phase 1
NCT01147549 Completed Healthy AstraZeneca June 2010 Phase 1
NCT01054170 Completed Chronic Obstructive Pulmonary Disease (COPD) AstraZeneca January 2010 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID