GW-311616 is a potent, orally bioavailable, long duration and selective human neutrophil elastase ( HNE ) inhibitor with IC 50 value of 22 nM and K i value of 0.31 nM.
Storage Temp
Store at -20°C
Shipped In
Ice chest + Ice pads
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Product Description
GW-311616 is a potent, orally bioavailable, long duration and selective human neutrophil elastase ( HNE ) inhibitor with IC 50 value of 22 nM and K i value of 0.31 nM
In Vitro
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. GW-311616 (150 μM; U937 cells) treatment can increase the protein expression levels of Bax and decrease the expression of Bcl-2. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: U937 and K562 cells Concentration: 150 μM Incubation Time: 48 hours Result: Markedly suppressed NE activity. Apoptosis AnalysisCell Line: U937 cells Concentration: 20 μM, 40 μM, 80 μM, 160 μM, 320 μM Incubation Time: 48 hours Result: The rate of apoptosis was enhanced. Western Blot AnalysisCell Line: U937 cells Concentration: 150 μM Incubation Time: 48 hours Result: Increased the protein expression levels of Bax and decreased the expression of Bcl-2.
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 (t 1/2 ) of 1.1 hours and 1.5 hours for dog (2 mg/kg, oral), rat (2 mg/kg, oral), respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Dogs (9-month-old)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 was achieved 6 hours after dosing, with activity returning towards control values. Single oral dose of 2 mg/kg rapidly abolished circulating enzyme activity, and greater than 90% inhibition was maintained for 4 days.
This compound belongs to the class of organic compounds known as n-acylpyrrolidines. These are n-Acylated Pyrrolidine derivatives. Pyrrolidine is a five-membered saturated aliphatic heterocycle with one nitrogen atom and four carbon atoms.
External Descriptors
Not available
1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.
