NLRP3-IN-10 是一种强效的NLRP3抑制剂，抑制 IL-1β 的IC50为 251.1 nM。NLRP3-IN-10 能够减弱ASC斑点形成抑制NLRP3炎症小体激活。
| 生物活性 | NLRP3-IN-10 is a potentNLRP3 inhibitor, inhibits IL-1β release with anIC50value of 251.1 nM. NLRP3-IN-10 suppressesNLRP3inflammasome activation by attenuating ASC speck formation[1]. |
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体外研究
(In Vitro) | 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[1].
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) avoidsNigericin(HY-127019)-induced pyroptosis[1].
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[1].
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>[1].
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[1].
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体内研究
(In Vivo) | 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[1].
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[1].
Pharmacokinetics of NLRP3-IN-10 in mouse[1]
| Route | Dose (mg/kg) | AUC0-t(μg·h/L) | CL (L/h/kg) | Cmax(μg/L) | T1/2(h) | Tmax(h) | F (%) | | IV | 10 | 105.88 | 133.75 | 81.97 | 3.13 | 0.11 | | | PO | 10 | 14.60 | 2201.58 | 3.35 | 7.43 | 2.11 | 13.79 | | PO | 30 | 15.84 | 2583.27 | 16.42 | 7.92 | 1.26 | 4.99 | | PO | 90 | 23.53 | 5551.12 | 13.59 | 6.08 | 4.21 | 2.47 |
| Animal Model: | MSU-induced peritonitis in a LPS-primed mouse model (C57BL/6J mice, 7-week-old, male)[1]
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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
