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Chemical Structure| 1638611-48-9 Chemical Structure| 1638611-48-9

Structure of JC124
CAS No.: 1638611-48-9

Chemical Structure| 1638611-48-9

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JC124 is a specific NLRP3 inflammasome inhibitor with anti-inflammatory and neuroprotective effects.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Citations

Product Citations

Zhang, Peng ; Li, Zhipeng ; Liang, Minxue ; Yuan, Jinxian ; Zhou, Jinyu ; Zhang, Jie , et al.

Abstract: Background: Despite continuous development of antiseizure medications (ASMs), global seizure control rates remain unsatisfactory, highlighting the urgent need for novel ASMs targeting distinct pathophysiological mechanisms. Inhibition of NLRP3 inflammasome activation represents an emerging strategy to simultaneously attenuate seizures and associated neuropsychiatric comorbidities. Therefore, this study investigates whether JC124, a novel NLRP3 inflammasome inhibitor, exerts neuroprotective effects in kainic acid (KA)-induced epileptic mice and in human induced pluripotent stem cell (hiPSC)-derived neurons stimulated by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Methods: Summary-based Mendelian Randomization (SMR) was used to analyze the association between NLRP3 alleles and epilepsy susceptibility. NLRP3 knockout mice were generated, and then epileptic mice induced by intrahippocampal KA injection were administered JC124 (50 mg/kg, intraperitoneal) once daily for 28 days. The spontaneous recurrent seizures, hippocampal local field potential, depressive-like behavior, cognitive dysfunction, and locomotor ability of mice were evaluated. The brain tissues of the mice were collected for Western blotting, immunohistochemistry, immunofluorescence labeling, enzyme-linked immunosorbent assay, transmission electron microscopy, and morphological staining. The binding capacity of JC124 to the human NLRP3 protein was assessed using molecular docking and molecular dynamics simulations. hiPSC-derived neurons were used to explore the neuroprotective effects of JC124 against inflammatory injury in human neurons. Results: In this study, a positive correlation was identified between the expression of the NLRP3 gene and the susceptibility to epilepsy through SMR analysis. JC124 intervention markedly inhibited seizures and improved depressive-like behavior and cognitive dysfunction. It also reduced hippocampal neuronal loss, neuronal pyroptosis, microgliosis, and astrogliosis. Importantly, the neuroprotective effects of JC124 in KA-induced epileptic mice were mediated through the inhibition of the NLRP3 inflammasome. JC124 inhibited neuroinflammation and oxidative stress in KA-treated NLRP3 wild-type mice, but not in KA-treated NLRP3 knockout mice. Furthermore, JC124 bound directly to the human NLRP3 protein and alleviated neuroinflammation and oxidative stress in hiPSC-derived neurons stimulated by LPS and ATP. Conclusions: These findings indicate that inhibiting the activation of the NLRP3 inflammasome with JC124 represents a potentially safe and innovative therapeutic strategy to mitigate neuroinflammation and oxidative stress in epilepsy and to alleviate seizures and associated neuropsychiatric comorbidities.

Keywords: JC124 ; Epilepsy ; Neuropsychiatric comorbidities ; NLRP3 inflammasome ; Neuroinflammation ; Oxidative stress

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Product Details of JC124

CAS No. :1638611-48-9
Formula : C17H19ClN2O4S
M.W : 382.86
SMILES Code : O=C(NCCC1=CC=C(S(=O)(NC)=O)C=C1)C2=CC(Cl)=CC=C2OC
English Name :5-Chloro-2-methoxy-N-(4-(N-methylsulfamoyl)phenethyl)benzamide
MDL No. :N/A
InChI Key :LXYPQRJNQPYTQW-UHFFFAOYSA-N
Pubchem ID :117715670

Safety of JC124

Isoform Comparison

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.61mL

0.52mL

0.26mL

13.06mL

2.61mL

1.31mL

26.12mL

5.22mL

2.61mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

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