产品
编 号：F741695
分子式：C17H14BrFO3
分子量：365.19
分子式：C17H14BrFO3
分子量：365.19
产品类型
规格
价格
是否有货
5mg
询价
询价
10mg
询价
询价
25mg
询价
询价
50mg
询价
询价
100mg
询价
询价
结构图
CAS No: 2641826-39-1
产品详情
生物活性：
NLRP3-IN-10 is a potent NLRP3?inhibitor, inhibits IL-1β release with an IC50 value of 251.1 nM. NLRP3-IN-10 suppresses NLRP3 inflammasome activation by attenuating ASC speck formation.
体内研究：
NLRP3-IN-10 (compound 14c) (10 mg/kg; i.v.; single dose) reduces peritoneal neutrophil influx in mice and IL-1β in the spleen in the MSU-induced peritonitis in LPS-primed mouse model.NLRP3-IN-10 (10, 30, 90 mg/kg; p.o.; single dose) exhibits extremely low exposure (14.6?23.53 μg·h/L), poor bioavailability (2.47?13.79%), and high plasma clearance (2201.58?5551.12 L/h/kg) after different doses for oral administration.Pharmacokinetics of NLRP3-IN-10 in mouseRouteDose (mg/kg)AUC0-t (μg·h/L)CL (L/h/kg)Cmax (μg/L)T1/2 (h)Tmax (h)F (%)
IV10105.88133.7581.973.130.11
PO1014.602201.583.357.432.1113.79
PO3015.842583.2716.427.921.264.99
PO9023.535551.1213.596.084.212.47
Animal Model:MSU-induced peritonitis in a LPS-primed mouse model (C57BL/6J mice, 7-week-old, male)LPS: 1 mg/kg, i.p.; MSU: 100 mg/kg, i.v.
Dosage:10 mg/kg
Administration:Intravenous injection; single dose
Result:Significantly reduced IL-1β release in the spleen of mice after 6 h treatment.Significantly reduced the increase of peritoneal neutrophil influx compared with the control group.
体外研究：
NLRP3-IN-10 (compound 14c) (0.4, 1.6, 6.4 μM; 40 min) exerts remarkable inhibitory activity on NLRP3 inflammasome activation induced by LPS-MSU (12 h) in THP-1 cells in a dose-dependent manner. NLRP3-IN-10 (0.1-6.4 μM; 1.5 h) shows no cytotoxicity against THP-1 cells and (0.1, and 0.4 μM; 40 min) avoids Nigericin (HY-127019)-induced pyroptosis.NLRP3-IN-10 (0.1, 0.2, and 0.4 μM; 40 min) reduces the processing of caspase-1 p20 and IL-1β, in supernatants in THP-1 cells in a dose-dependent manner.NLRP3-IN-10 (3 μM and 5 μM; 40 min) decreases LPS-induced THF-α, and (0.2 μM and 0.8 μM; 40 min) reduces the rate of THP-1 cells with ASC specks, indicating ASC oligomerization interruptionsup>.NLRP3 inflammasome is regarded as a two-step process, including priming and action. NLRP3-IN-10 (1, 10, and 100 μM; 40 min) suppresses LPS-induced NLRP3 priming through directly interacting with NLRP3.
NLRP3-IN-10 is a potent NLRP3?inhibitor, inhibits IL-1β release with an IC50 value of 251.1 nM. NLRP3-IN-10 suppresses NLRP3 inflammasome activation by attenuating ASC speck formation.
体内研究：
NLRP3-IN-10 (compound 14c) (10 mg/kg; i.v.; single dose) reduces peritoneal neutrophil influx in mice and IL-1β in the spleen in the MSU-induced peritonitis in LPS-primed mouse model.NLRP3-IN-10 (10, 30, 90 mg/kg; p.o.; single dose) exhibits extremely low exposure (14.6?23.53 μg·h/L), poor bioavailability (2.47?13.79%), and high plasma clearance (2201.58?5551.12 L/h/kg) after different doses for oral administration.Pharmacokinetics of NLRP3-IN-10 in mouseRouteDose (mg/kg)AUC0-t (μg·h/L)CL (L/h/kg)Cmax (μg/L)T1/2 (h)Tmax (h)F (%)
IV10105.88133.7581.973.130.11
PO1014.602201.583.357.432.1113.79
PO3015.842583.2716.427.921.264.99
PO9023.535551.1213.596.084.212.47
Animal Model:MSU-induced peritonitis in a LPS-primed mouse model (C57BL/6J mice, 7-week-old, male)LPS: 1 mg/kg, i.p.; MSU: 100 mg/kg, i.v.
Dosage:10 mg/kg
Administration:Intravenous injection; single dose
Result:Significantly reduced IL-1β release in the spleen of mice after 6 h treatment.Significantly reduced the increase of peritoneal neutrophil influx compared with the control group.
体外研究：
NLRP3-IN-10 (compound 14c) (0.4, 1.6, 6.4 μM; 40 min) exerts remarkable inhibitory activity on NLRP3 inflammasome activation induced by LPS-MSU (12 h) in THP-1 cells in a dose-dependent manner. NLRP3-IN-10 (0.1-6.4 μM; 1.5 h) shows no cytotoxicity against THP-1 cells and (0.1, and 0.4 μM; 40 min) avoids Nigericin (HY-127019)-induced pyroptosis.NLRP3-IN-10 (0.1, 0.2, and 0.4 μM; 40 min) reduces the processing of caspase-1 p20 and IL-1β, in supernatants in THP-1 cells in a dose-dependent manner.NLRP3-IN-10 (3 μM and 5 μM; 40 min) decreases LPS-induced THF-α, and (0.2 μM and 0.8 μM; 40 min) reduces the rate of THP-1 cells with ASC specks, indicating ASC oligomerization interruptionsup>.NLRP3 inflammasome is regarded as a two-step process, including priming and action. NLRP3-IN-10 (1, 10, and 100 μM; 40 min) suppresses LPS-induced NLRP3 priming through directly interacting with NLRP3.
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