CS-1261

生物活性靶点体外研究体内研究 CS-1261 试剂级价格

CS-1261

CAS号:198062-54-3
英文名:(3S,3AS,6AR)-3-ISOPROPYL-1-(METHANESULFONYL)-4-[4-(1-PIPERIDINYL)-2(E)-BUTENOYL]PERHYDROPYRROLO[3,2B]PYRROL-2(1H)-ONE HYDROCHLORIDE
中文名:CS-1261
CBNumber:CB2420576
分子式:C19H31N3O4S
分子量:397.53
MOL File:198062-54-3.mol

CS-1261化学性质

沸点 :583.6±60.0 °C(Predicted)
密度 :1.27±0.1 g/cm3(Predicted)
储存条件 :2-8°C
溶解度 :H₂O: 24 mg/mL, soluble
形态 :solid
酸度系数(pKa) :8.53±0.10(Predicted)
颜色 :Light brown to brown

安全信息

危险品标志 :Xi
危险类别码 :36/37/38
安全说明 :26-36
WGK Germany :3

CS-1261性质、用途与生产工艺

生物活性 GW-311616 是高活性，口服生物相容性，长效的人中性白细胞弹性蛋白酶 (HNE) 抑制剂。IC50 为 22 nM，Ki 为 0.31 nM。
靶点

IC50: 22 nM (HNE) Ki: 0.31 nM (HNE)

体外研究

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.

Cell Viability Assay

Cell Line:	U937 and K562 cells
Concentration:	150 μM
Incubation Time:	48 hours
Result:	Markedly suppressed NE activity.

Apoptosis Analysis

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

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.

体内研究

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 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.