GW311616

小分子

GW 311616 | L8012V52PN | MS-26715 | PYRROLO(3,2-B)PYRROL-2(1H)-ONE, HEXAHYDRO-3-(1-METHYLETHYL)-1-(METHYLSULFONYL)-4-(1-OXO-4-(1-PIPERIDINYL)-2-BUTENYL)-, (3S-(3.ALPHA.,3A.ALPHA.,4(E),6A.BETA.))- | (3aR,6S,6aS)-4-methylsulfonyl-1-[(E)-4-piperidin-1-ylbut-

GW311616

G647148-5mg

5mg

≥99%

-20°C储存

超低温冰袋运输

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. Form:Solid IC50& Target:IC50: 22 nM (HNE), Ki: 0.31 nM (HNE)

GW-311616 是一种强效、口服生物利用度高、持续时间长且具有选择性的人中性粒细胞弹性蛋白酶（HNE）抑制剂，其 IC 50 值为 22 nM，K i 值为 0.31 nM。

198062-54-3

C19H31N3O4S

397.53 g/mol

9800961

CC(C)[C@H]1[C@H]2[C@@H](CCN2C(=O)/C=C/CN3CCCCC3)N(C1=O)S(=O)(=O)C

(3aR,6S,6aS)-4-methylsulfonyl-1-[(E)-4-piperidin-1-ylbut-2-enoyl]-6-propan-2-yl-3,3a,6,6a-tetrahydro-2H-pyrrolo[3,2-b]pyrrol-5-one

1S/C19H31N3O4S/c1-14(2)17-18-15(22(19(17)24)27(3,25)26)9-13-21(18)16(23)8-7-12-20-10-5-4-6-11-20/h7-8,14-15,17-18H,4-6,9-13H2,1-3H3/b8-7+/t15-,17+,18-/m1/s1

NDNKNUMSTIMSHQ-URZKGLGPSA-N

CC(C)C1C2C(CCN2C(=O)C=CCN3CCCCC3)N(C1=O)S(=O)(=O)C

9800961

198062-54-3

GW 311616;GW311616;GW311616A

DMSO : 66.67 mg/mL (167.71 mM; Need ultrasonic)

0

5

5

397.204 Da

397.204 Da

86.400 Ų

27

0

707.000

0

1

1.300