[CAS NO. 197890-44-1] GW311616hydrochloride
PRODUCTS SPECIFICATIONS [197890-44-1]
DESCRIPTION [197890-44-1]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 433.99 |
| Molecular Formula | C19H32ClN3O4S |
| SMILES | O=C1[C@@H](C(C)C)[C@@](N(C(/C=C/CN2CCCCC2)=O)CC3)([H])[C@]3([H])N1S(=O)(C)=O.[H]Cl |
6 Publications Citing Use of MCE
Summary
In Vitro
GW-311616 (150 μM; 48 hours) markedly suppresses NE activity in U937 and K562 cells lines
[2]
.
GW311616A (20-320 μM; 48 hours; U937 cells) treatment inhibits proliferation and induces apoptosis in leukemia cells
[2]
.
GW-311616 (150 μM; U937 cells) treatment can increase the protein expression levels of Bax and decrease the expression of Bcl-2
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [2]
| Cell Line: | U937 and K562 cells |
| Concentration: | 150 μM |
| Incubation Time: | 48 hours |
| Result: | Markedly suppressed NE activity. |
Apoptosis Analysis [2]
| Cell 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. |
| Cell 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 [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 100 mg/mL ( 230.42 mM ; Need ultrasonic)
H 2 O : 100 mg/mL ( 230.42 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3042 mL | 11.5210 mL | 23.0420 mL |
| 5 mM | 0.4608 mL | 2.3042 mL | 4.6084 mL |
| 10 mM | 0.2304 mL | 1.1521 mL | 2.3042 mL |
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.
