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E6446 dihydrochloride is a potent and orally acitve antagonist of TLR7 and TLR9. E6446 dihydrochloride is also a potent SCD1 inhibitor (KD: 4.61 μM), significantly inhibiting adipogenic differentiation and hepatic lipogenesis through SCD1-ATF3 signaling.
In vitro, low doses of E6446 specifically inhibited the activation of human and mouse TLR9. E6446 suppress TLR9-DNA interaction in vitro, with an IC50 in the 1 to 10 µM range. E6446 reduces 50% of TLR4 activation at 30 μM, and shows IC50s of 0.01 μM and 0.23 μM in HEK-TLR9 cells stimulated with oligo 2006 and in human PBMCs stimulated with oligo 2216, respectively.
In vivo, therapy with E6446 diminished the activation of TLR9 and prevented the exacerbated cytokine response observed during acute Plasmodium infection. E6446 (20, 60 mg/kg, p.o.) dose-dependently inhibits TLR9 signaling in mice.
| Molecular Weight | 522.51 |
| Formula | C27H37Cl2N3O3 |
| CAS Number | 1345675-25-3 |
| Solubility (25°C) | DMSO 5.2 mg/mL (Need ultrasonic and warming) |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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