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GW311616 is a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase(HNE) with IC50 of 22 nM. GW311616 is the free base form of GW311616A. The HNE inhibitor GW311616A is selective over other human serine proteases (IC50 values >100 uM for trypsin, cathepsin G, and plasmin, >3 mM for chymotrypsin and tissue plasminogen activator). Acetylcholinesterase is not inhibited by GW311616A at 100 uM.
GW-311616 (2 mg/kg; oral administration) rapidly abolishes the circulation of neutrophil elastase (NE) in dogs, while >90% inhibition is maintained for 4 days. This prolonged effect is independent to be due to penetration of neutrophils in bone marrow by orally administrated GW-311616. GW-311616 has moderate terminal elimination half-life (t1/2) of 1.1 hours and 1.5 hours for dog (2 mg/kg, oral), rat (2 mg/kg, oral), respectively.
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Source | Mol Med Rep (2015). Figure 4. GW311616 |
| Method | proliferation assay | |
| Cell Lines | U937 cells | |
| Concentrations | 150 μmol/l | |
| Incubation Time | 48 h | |
| Results | In the GW311616A.treated group, the rate of apoptosis was enhanced, as compared with the control group |
| Molecular Weight | 397.53 |
| Formula | C19H31N3O4S |
| CAS Number | 198062-54-3 |
| Solubility (25°C) | DMSO 50 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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MeOSuc-Ala-Ala-Pro-Met-AMC is a peptide substrate of elastases and chymotrypsin-like serine peptidases. |
| Suc-Ala-Ala-Pro-Val-AMC
Suc-Ala-Ala-Pro-Val-AMC, a tetrapeptide, is an elastasesubstrate. |
| Suc-Ala-Ala-Ala-AMC
Suc-Ala-Ala-Ala-AMC is a peptide substrate of elastase or elastase-like. |
| Suc-Ala-Pro-Ala-AMC
Suc-Ala-Pro-Ala-AMC is a tripeptide substrate of elastase. |
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