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TJ-M2010-5 is a MyD88 inhibitor that binds to the TIR domain of MyD88 to interfere with its homodimerization, and the TLR/MyD88 signal pathway. TJ-M2010-5 inhibited MyD88 homodimerization in transfected HEK293 cells in a concentration-dependent manner and suppressed MyD88 signaling in LPS-responsive RAW 264.7 cells in vitro.
In a 10-week CAC mouse model (n = 30 per group), TJ-M2010-5 treatment statistically significantly reduced AOM/DSS-induced colitis and completely prevented CAC development with less related body mass loss, resulted in 0% mortality of treated mice (compared with 53% mortality of control mice), decreased cell proliferation, and increased apoptosis in colon tissue. TJ-M2010-5 treatment also inhibited production of inflammatory cytokines and chemokines (TNF-α, IL-6,G-CSF, MIP-1β, TGF-β1, IL-11, IL-17A, IL-22 and IL-23) and infiltration of immune cells (macrophages, dendritic cells, neutropihls and CD(+)4 T cells) in colon tissues of mice.
| Cell Experiment | |
|---|---|
| Cell lines | RAW 264.7 cells |
| Preparation method | RAW 264.7 cells were cultured in RPMI medium 1640. After stimulation with 100ng/mL of lipopolysaccharide (LPS) for six hours with 40 µM TJ-M2010-5 or vehicle one hour pretreatment, cells in individual wells were harvested for protein extraction. |
| Concentrations | 40 µM |
| Incubation time | 6 hours |
| Animal Experiment | |
|---|---|
| Animal models | Female BalB/c mice (6–8 weeks old) |
| Formulation | vehicle (ddH2 O) |
| Dosages | 50mg/Kg daily |
| Administration | i.p. |
| Molecular Weight | 406.54 |
| Formula | C23H26N4OS |
| CAS Number | 1357471-57-8 |
| Solubility (25°C) | DMSO 90 mg/mL |
| Storage | 4°C, protect from light, sealed |
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