Details
Stereochemistry | ACHIRAL |
Molecular Formula | C25H22F3N5O4S |
Molecular Weight | 545.533 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1N=CC=C1C2=C(C)N(C(=O)C(=C2)C(=O)NCC3=NC=C(C=C3)S(C)(=O)=O)C4=CC(=CC=C4)C(F)(F)F
InChI
InChIKey=QNQZWEGMKJBHEM-UHFFFAOYSA-N
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)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21791628Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22267768 |
https://www.ncbi.nlm.nih.gov/pubmed/23391369 |
https://clinicaltrials.gov/ct2/show/NCT02597101?term=AZD-9668&phase=1&rank=8
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21791628
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22267768 |
https://www.ncbi.nlm.nih.gov/pubmed/23391369 |
https://clinicaltrials.gov/ct2/show/NCT02597101?term=AZD-9668&phase=1&rank=8
Avelestat, also known as AZD9668, 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, Cystic Fibrosis and chronic obstructive pulmonary disease via its role in the inflammatory process, mucus overproduction, and lung tissue damage. Its development was discontinued due to unknown reasons. Nevertheless, this drug in the phase II of clinical trial as adjunctive therapy in improving insulin sensitivity of insulin-resistant type 2 diabetic subjects. The drug's clinical profile suggests that it will be well tolerated with few, if any, side effects, and the existence of simple methods that can indirectly measure its activity in vivo.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL248 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21791628 |
12.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Palliative | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
621.7 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22458939 |
60 mg 2 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ALVELESTAT plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
60 mg 2 times / day steady-state, oral Studied dose Dose: 60 mg, 2 times / day Route: oral Route: steady-state Dose: 60 mg, 2 times / day Sources: Page: p.117 |
unhealthy, ADULT n = 202 Health Status: unhealthy Condition: COPD Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 202 Sources: Page: p.117 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22267768
2 x 30 mg oral tablets twice daily (bid) for 12 weeks
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21791628
In cell-based assays, AZD9668 inhibited plasma Neutrophil elastase (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.
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NCI_THESAURUS |
C783
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FDA ORPHAN DRUG |
804020
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848141-11-7
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C125714
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6Y5629322X
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100000156677
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DB11863
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DTXSID40233875
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C568080
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46861623
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9391
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SUB130609
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)