| Description | GW-311616 is a long duration, orally bioavailable, and selective human neutrophil elastase (HNE) inhibitor (IC50: 22 nM; Ki: 0.31 nM). |
| In vitro | GW-311616 (150 μM;?U937 cells) treatment can increase the protein expression levels of Bax and decrease the expression of Bcl-2.GW-311616 (150 μM; 48 hours) markedly suppresses NE activity in U937 and K562 cells lines. GW-311616 (20-320 μM; 48 hours; U937 cells) treatment inhibits proliferation and induces apoptosis in leukemia cells. |
| In vivo | 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.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. |
| Target activity | HNE:(ki)0.31 nM , HNE:22 nM |
| molecular weight | 397.53 |
| Molecular formula | C19H31N3O4S |
| CAS | 198062-54-3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 44 mg/mL (110.68 mM) |
| References | 1. Ohbayashi H,et al. Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80. 2. Jiang KL, et al. Neutrophil elastase and its therapeutic effect on leukemia cells. Mol Med Rep. 2015 Sep;12(3):4165-4172. 3. Macdonald SJ, et al. 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. |