Biological Activity
SC75741 is a broad and efficient NF-κB inhibitor with an IC50 of 200 nM for p65[1]. SC75741 blocks influenza viruses (IV) replication in non-toxic concentrations. SC75741 impairs DNA binding of the NF-κB subunit p65, resulting in reduced expression of cytokines, chemokines, and pro-apoptotic factors. SC75741 subsequently inhibits caspase activation and blocks caspase-mediated nuclear export of viral ribonucleoproteins[2].
In Vitro
SC75741 (1-10 μM; 5.5-65 hours) reduces A549 cells viability in a concentration-dependent manner indicating a cytostatic effect within a time frame of about 50 and 65 hours[2]. SC75741 (5 μM; 24 hours) strongly inhibits cleavage of the effector caspase 3 induced upon H7N7-infection[2]. Cell Viability Assay[2] Cell Line: A549 cells Concentration: 1, 2, 5 or 10 μM Incubation Time: 5.5, 29, 50, 65 hours Result: Cells viability was reduced in a concentration-dependent manner indicating a cytostatic effect. Western Blot Analysis[2] Cell Line: MDCK cells Concentration: 5 μM Incubation Time: 24 hours Result: Inhibited cleavage of the effector caspase 3 induced upon H7N7-infection.
In Vivo
SC75741 (intraperitoneal injection; 15 mg/kg; for 2 days) leads to a reduced propagation of the H5N1 virus in the lungs of infected mice[2]. The plasma-levels of SC74751 (intravenously of 5 mg/kg and intraperitoneally of 15 mg/kg; for 3.5 and 6 hours) after i.v. administration decreases mono-exponentially and half-life is roughly 40 min. After i.p. administration, elimination of SC75741 seems to be limited by a slow uptake from the peritoneum and a half-life of 55 min is observed[1]. Animal Model: Inbred female C57BL/6 mice at the age of 6-8 weeks[2] Dosage: 15 mg/kg Administration: Intraperitoneal injection; for 2 days Result: The amount of viral mRNA was reduced by 90%. Animal Model: Inbred female C57BL/6 mice at the age of 6-8 weeks[1] Dosage: 5 mg/kg or 15 mg/kg Administration: Intravenously of 5 mg/kg and intraperitoneally of 15 mg/kg; 3.5 and 6 hours Result: Half-life was roughly 40 min and 55 min for i.v. and i.p. administration, respectively.
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
