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SC75741 is a potent NF-κB inhibitor with EC50 value of 200 nM. NF-kB is a protein complex that regulates the expression of immunoreceptors, inflammatory cytokines and chemokines and is commonly regarded as a major antiviral factor. However, it has been shown that influenza A viruses exploit this signaling pathway for efficient replication [1].In MDCK cells, inhibitory potential of 5 uM SC75741 on virus replication is highest at later stages of infection. In the human alveolar type II epithelial cell line A549 infected with H5N1 and H7N7 viruses, SC75741 provoked an efficient reduction of virus titers in a dose-dependent way [1].In the lung of infected mice, SC75741 reduces viral replication and H5N1-induced IL6 and IP-10 expression. In addition, SC75741 also reduced cytokine production in vivo that is involved in hypercytokinemia mediated by influenza virus infection. Importantly, SC75741 exhibits a high barrier for virus variants [1]. References:[1]. Ehrhardt C, Rückle A, Hrincius ER, et al. The NF-κB inhibitor SC75741 efficiently blocks influenza virus propagation and confers a high barrier for development of viral resistance. Cell Microbiol, 2013, 15(7): 1198-1211.
Cell lines
Epithelial Madin–Darbycanine kidney cells (MDCK)
Preparation method
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition
1 μM, 2 μM or 5 μM, 24 h
Applications
In Epithelial Madin–Darbycanine kidney cells (MDCK), SC75741 dose-dependently inhibited virus propagation. Treatment of MDCK cells with SC75741 (5 μM) inhibited virus replication in mono- and multicyclic infections with highest efficiency at later stages of infection replication of influenza A and B viruses. SC75741 exhibited antiviral activity on H1N1 and H3N2 influenza A virus subtype and influenza B virus replication. In the human alveolar type II epithelial cell line A549, SC75741 provoked an efficient reduction of progeny virus titres in a concentration-dependent manner. Prolonged treatment with SC75741 (55 h and 65 h) reduced cell viability in a concentration-dependent manner. SC75741 (5 μM) inhibited transcriptional activation of NF-kB-dependent genes. SC75741 (5 μM) reduced virus-induced expression of the NF-kB target genes IL-6 and TRAIL but not IFN-b or IRF-3 activity. SC75741 (5 μM) showed a high barrier for development of resistant virus variants.
Animal models
C57BL/6 mice
Dosage form
Intraperitoneal administration, 15 mg/kg
Application
SC75741 (15 mg/kg, i.p.) reduced virus replication and cytokine expression in mice lungs after H5N1 influenza virus infection.
Other notes
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References:
[1]. Ehrhardt C, Rückle A, Hrincius E R, et al. The NF‐κB inhibitor SC75741 efficiently blocks influenza virus propagation and confers a high barrier for development of viral resistance[J]. Cellular microbiology, 2013, 15(7): 1198-1211.
