NLRP3-IN-10

• CAT Number: I042861
• CAS Number: 2641826-39-1
• Molecular Formula: C17H14BrFO3
• Molecular Weight: 365.19
• Purity: ≥95%
• Synonyms: (E)-3-(4-bromo-2,5-dimethoxyphenyl)-1-(4-fluorophenyl)prop-2-en-1-one
• InChI: InChI=1S/C17H14BrFO3/c1-21-16-10-14(18)17(22-2)9-12(16)5-8-15(20)11-3-6-13(19)7-4-11/h3-10H,1-2H3/b8-5+
• InChIKey: ZXMIFRJYIRYWTC-VMPITWQZSA-N
• SMILES: COC1=CC(=C(C=C1C=CC(=O)C2=CC=C(C=C2)F)OC)Br

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[1].
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) avoids Nigericin (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].
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

Reference

[1]. Zhang R, et al. New Highly Potent NLRP3 Inhibitors: Furanochalcone Velutone F Analogues. ACS Med Chem Lett. 2022 Mar 7;13(4):560-569.
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