CS-1260
| 中文名称 | CS-1260 |
|---|---|
| 中文同义词 | 化合物 T11525L;化合物 GW311616 HYDROCHLORIDE |
| 英文名称 | GW311616A |
| 英文同义词 | CS-1260;GW 311616A;GW-311616A;GW 311616A - GW 311616 hydrochloride;GW311616 hydrochloride,GW-311616 hydrochloride |
| CAS号 | 197890-44-1 |
| 分子式 | C19H32ClN3O4S |
| 分子量 | 433.99 |
| EINECS号 | |
| 相关类别 | |
| Mol文件 | 197890-44-1.mol |
| 结构式 |  |
CS-1260 性质
| 储存条件 | 2-8°C |
|---|---|
| 溶解度 | H2O：24 mg/mL，可溶 |
| 形态 | 固体 |
| 颜色 | 白色至黄色 |
IC50: 22 nM (HNE) Ki: 0.31 nM (HNE)
GW-311616 (150 μM; 48 hours) markedly suppresses NE activity in U937 and K562 cells lines.
GW311616A (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.
Cell Viability Assay
| 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. |
Western Blot Analysis [2]
| 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. |
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.
| 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 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. |