Nuclear Factor-kappa B (NF-κB) is a transcription factor family that regulates a large number of genes that are involved in important physiological processes, including survival, inflammation, and immune responses[3]. SC75741 is a potent inhibitor of NF-κB with an EC50 of 200 nM[2]. SC75741 also acts as a broad and efficient blocker of IV replication in non-toxic concentrations. The underlying molecular mechanism of SC75741 action involves impaired DNA binding of the NF-κB subunit p65, resulting in reduced expression of cytokines, chemokines, and pro-apoptotic factors, subsequent inhibition of caspase activation and block of caspase-mediated nuclear export of viralribonucleoproteins. SC75741 reduces viral replication and H5N1-induced IL-6 and IP-10 expression in the lung of infected mice. Besides its virustatic effect the drug suppresses virus-induced overproduction of cytokines and chemokines, suggesting that it might prevent hypercytokinemia that is discussed to be an important pathogenicity determinant of highly pathogenic IV. Importantly the drug exhibits a high barrier for development of resistant virus variants. Thus, SC75741-derived drugs may serve as broadly non-toxic anti-influenza agents[1].
SC75741 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293WT cells
5 µM
6-12 hours
SC75741 enhanced autophagy activity
Front Pharmacol. 2021 Oct 29;12:741219
LLC-PK cells
20 µM
24 hours
SC75741 inhibited PDCoV infection
Int J Mol Sci. 2022 Mar 18;23(6):3280
SH-SY5YGT25 cells
5 µM
24 hours
SC75741 promoted TDP25 degradation
Front Pharmacol. 2021 Oct 29;12:741219
H4GT25 cells
5 µM
24 hours
SC75741 significantly reduced TDP25 protein levels
Front Pharmacol. 2021 Oct 29;12:741219
OCCM-30 cells
5 µM
2 hours
Inhibited the NF-κB pathway, reduced NLRP3 expression and pyroptosis in P. gingivalis-infected OCCM-30 cells
Heliyon. 2024 May 7;10(9):e30814
Duck primary monocytes/macrophages
1 µMol/mL
24 hours
Evaluate the antiviral activity of SC75741 in duck monocytes/macrophages. Results showed that SC75741 significantly inhibited DPV replication.
Poult Sci. 2021 May;100(5):101085
Duck primary astrocytes
5 µMol/mL
24 hours
Evaluate the antiviral activity of SC75741 in duck astrocytes. Results showed that SC75741 significantly inhibited VSV-GFP and DTMUV replication but had no effect on DPV.
Poult Sci. 2021 May;100(5):101085
Duck primary neurons
5 µMol/mL
24 hours
Evaluate the antiviral activity of SC75741 in duck neurons. Results showed that SC75741 significantly inhibited VSV-GFP and DTMUV replication.
Poult Sci. 2021 May;100(5):101085
T24 cells
5 µM
24 hours
Inhibition of NF-κB signaling pathway, reducing clonogenic survival and invasion capability of bladder cancer cells.
J Clin Med. 2019 Nov 13;8(11):1954
MB49 cells
5 µM
24 hours
Inhibition of NF-κB signaling pathway, reducing clonogenic survival and invasion capability of bladder cancer cells.
J Clin Med. 2019 Nov 13;8(11):1954
Duck embryo fibroblast cells (DEF)
0.2–50 µMol/mL
24, 48, or 72 hours
Evaluate the antiviral activity of SC75741 against VSV-GFP, DTMUV, and DPV-GFP. Results showed that SC75741 significantly inhibited viral replication in a dose-dependent manner.
Poult Sci. 2021 May;100(5):101085
SW982 cells
2 µM
48 hours
Inhibited the expression of NF-κB and α-SMA, reduced levels of inflammatory markers TNF-α and IL-6
Int J Mol Sci. 2021 Oct 14;22(20):11082
Human nucleus pulposus cells
5 µM
6 and 12 hours
To investigate the inhibitory effect of SC75741 on the NF-κB signaling pathway, results showed that SC75741 reversed rhS100A9-induced NP cell apoptosis, matrix degradation, and inflammatory response.
J Cell Mol Med. 2021 May;25(10):4709-4720
RAW264.7 cells
2 µM
Overnight
Reduced the population of TRAP+ multinucleated cells and downregulated MMP9, RANKL, TRAP, and OPG proteins
Int J Mol Sci. 2021 Oct 14;22(20):11082
SC75741 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Wistar rats
Papain-induced osteoarthritis model
Oral
15 mg/kg
Three times a week for 12 weeks
Ameliorated articular cartilage destruction, reduced OARSI scores, suppressed inflammatory markers NF-κB, TNF-α, IL-6, and miR-21, and promoted chondrogenesis inducers GDF-5, SOX5, TGF-β1, BMPR2, and COL4A1
Int J Mol Sci. 2021 Oct 14;22(20):11082
Nude mice (BALB/c-nu)
U251 cell xenograft tumor model
Intraperitoneal injection
5 mg/kg
Once daily for 3 weeks
Inhibit NF-κB activity and reverse RIP2 overexpression-induced TMZ resistance
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