CNI-1493 suppressed TNF translation through both 5' and 3' untranslated regions of TNF mRNA
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3967-71
Human peripheral blood mononuclear cells (PBMCs)
1 µM
1 hour
CNI-1493 inhibited LPS-stimulated TNF protein synthesis
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3967-71
Rat IEC-6 intestinal epithelioid cells
0.3 µM (IC50)
15 minutes
Inhibits TLR ligand-induced activation of p38 MAPK, NF-kB, and COX-2, but not activation by IL-1β or stresses.
J Immunol. 2016 Jun 15;196(12):5130-7
SH-SY5Y neuroblastoma cells
2.5 µM
15 minutes
To assess the effect of CNI-1493 on Aβ oligomer toxicity, results showed that CNI-1493 pretreatment completely abolished the toxicity of Aβ oligomers
J Exp Med. 2008 Jul 7;205(7):1593-9
HEK293 cells
10 µM
2 hours
Investigated the effect of Semapimod on gp96-TLR4 complexes, showing no effect on co-immunoprecipitation of gp96 and TLR4.
J Immunol. 2016 Jun 15;196(12):5130-7
SW480 enterocytes
2 µM
3 hours
Semapimod caused accumulation of TLR4 and TLR9 in perinuclear space, consistent with ER retention.
J Immunol. 2016 Jun 15;196(12):5130-7
Semapimod 4HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
Hepatoma model
Intraperitoneal injection
1 mg/kg/day
Once daily for 14 days
CNI-1493 markedly protected animals from IL-2 systemic toxicities whereas not affecting tumor response to IL-2 therapy.
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4561-6
Transgenic TgCRND8 mice
Alzheimer's disease model
Intraperitoneal injection
200 μg (8 mg/kg)
Twice a week for 8 weeks
To evaluate the effect of CNI-1493 on Aβ plaque formation and cognitive function, results showed that CNI-1493 significantly reduced Aβ plaque deposition and improved cognitive function in mice
J Exp Med. 2008 Jul 7;205(7):1593-9
Mice
Oxygen-induced retinopathy (OIR) model
Intraperitoneal injection
5 mg/kg
Once daily from P12 to P17
Inhibition of TNF-α significantly improves vascular recovery within ischemic tissue and reduces pathological neovascularization in OIR.
Am J Pathol. 2005 Feb;166(2):637-44
DA rats
Collagen-induced arthritis (CIA)
Intraperitoneal injection
5 mg/kg/day
Once daily until the end of the experiment
To investigate the protective effect of CNI-1493 on joint destruction in CIA rats. Results showed that CNI-1493 significantly reduced clinical signs of arthritis and cartilage destruction, and serum COMP levels were significantly lower in the CNI-1493 treated group.
Ann Rheum Dis. 2005 Mar;64(3):494-6
Adult male Lewis rats
Endotoxin-induced shock model
Intravenous and intracerebroventricular (i.c.v.)
Intravenous: 100 µg/kg to 500 µg/kg; i.c.v.: 0.1 ng/kg to 1000 ng/kg
Single dose, endotoxin administered 60 minutes later
To investigate the mechanism by which CNI-1493 inhibits endotoxin-induced TNF release and shock via the cholinergic antiinflammatory pathway. Results showed that i.c.v. administration was significantly more effective than intravenous dosing and required intact vagus nerve signaling.
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