| Identification | Back Directory | [Name]
GW311616A | [CAS]
197890-44-1 | [Synonyms]
CS-1260
GW 311616A;GW-311616A
GW 311616A - GW 311616 hydrochloride | [Molecular Formula]
C19Cl1H32N3O4S1 | [MDL Number]
MFCD06411566 | [MOL File]
197890-44-1.mol | [Molecular Weight]
433.99 |
| Hazard Information | Back Directory | [Description]
GW 311616A is an inhibitor of neutrophil elastase (IC50 = 100 nM). It is selective for neutrophil elastase (IC50 = 22 nM for the human enzyme) over trypsin, cathepsin G, and plasmin (IC50s = >100 μM for all), as well as chymotrypsin and tissue plasminogen activator (IC50s = >3 μM for both), in cell-free assays. GW 311616A (20 μM) inhibits the formation of neutrophil extracellular traps (NETs) induced by phorbol 12-myristate 13-acetate (PMA; ) in isolated human neutrophils. It inhibits intraneutrophil elastase activity in isolated dog blood six hours after administration of a 0.22 mg/kg dose. GW 311616A also inhibits neutrophil elastase in the liver in a mouse model of liver ischemia-reperfusion injury when administered at a dose of 2 mg/kg. | [Uses]
GW-311616 is a potent, orally bioavailable, long duration and selective human neutrophil elastase (HNE) inhibitor with IC50 value of 22 nM and Ki value of 0.31 nM[1]. | [in vivo]
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[3]. | Animal Model: | Dogs (9-month-old)[3] | | Dosage: | 0.22 mg/kg, 0.66 mg/kg and 2 mg/kg (Pharmacokinetic study) | | Administration: | Oral administration | | Result: | At 0.22 mg/kg, greater than 50% inhibition of elastase is achieved 6 hours after dosing, with activity returning towards control values. Single oral dose of 2 mg/kg rapidly abolishes circulating enzyme activity, and greater than 90% inhibition is maintained for 4 days.
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| [References]
[1] macdonald sj1, dowle md, harrison la, shah p, johnson mr, inglis gg, clarke gd, smith ra, humphreys d, molloy cr, amour a, dixon m, murkitt g, godward re, padfield t, skarzynski t, singh om, kumar ka, fleetwood g, hodgson st, hardy gw, finch h. the discovery of a potent, intracellular, orally bioavailable,long duration inhibitor of human neutrophil elastase-gw311616a a development candidate. bioorg med chem lett. 2001 apr 9;11(7):895-8. |
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| Company Name: |
SPIRO PHARMA
|
| Tel: |
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| Website: |
www.spiropharma.com.cn |
| Company Name: |
BOC Sciences
|
| Tel: |
16314854226 |
| Website: |
www.bocsci.com |
| Company Name: |
Musechem
|
| Tel: |
+1-800-259-7612 |
| Website: |
www.musechem.com |
| Company Name: |
Cckinase, Inc.
|
| Tel: |
+1 (732)236-3202 |
| Website: |
www.cckinase.com |
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