Uses
IAXO-102 is a TLR4 antagonist which negatively regulates TLR4 signalling. IAXO-102 inhibits MAPK and p65 NF-κB phosphorylation and expression of TLR4 dependent proinflammatory protein. IAXO-102 also prevents experimental abdominal aortic aneurysm development[1].
Biological Activity
IAXO-102 is a TLR4 antagonist targeting the MD-2 and CD14 co-receptors,which inhibits MAPK and p65 NF-κB phosphorylation and downregulates the expression of TLR4-dependent pro-inflammatory proteins. It inhibits the development of experimental abdominal aortic aneurysm (AAA).
in vitro
IAXO-102 (1-10 μM, for 2 hours) inhibits MAPK and p65 NF-κB phosphorylation in human umbilical vein endothelial (HUVEC) cells.
IAXO-102 (10 μM, for 17 hours) suppresses LPS induced proinflammatory proteins MCP-1 and IL-8 production in HUVEC.
Western Blot Analysis
| Cell Line: | Human umbilical vein endothelial (HUVEC) cells |
| Concentration: | 1-10 μM |
| Incubation Time: | Pretreatment for 1 hour and then exposed to LPS (100 ng/mL) for additional 1 hour |
| Result: | Significantly inhibited LPS- stimulated MAPK/p65nF-ΚB phosphorylation. |
in vivo
IAXO-102 (3 mg/kg/day, sc for 28 days) significantly retards Angiotensin II induced increase in aortic diameter in mice.
| Animal Model: < /td> | Six-monthold ApoE / /C57Bl6 |
| Dosage: | 3 mg/kg/day |
| Administration: | SC for 28 days |
| Result: | Significantly retarded Angiotensin II -induced increase in aortic diameter. |
target
| Target | Value |
TLR4
() |
MAPK
() |
NF-κB
() |
References
[1] Huggins C, et al. A novel small molecule TLR4 antagonist (IAXO-102) negatively regulates non-hematopoietic toll like receptor 4 signalling and inhibits aortic aneurysms development. Atherosclerosis. 2015 Oct;242(2):563-70. DOI:
10.1016/j.atherosclerosis.2015.08.010
