E6446

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

E6446 抑制 Toll 样受体 (TLR)7 和 9 信号传导。 E6446 在多种人类和小鼠细胞类型中发挥作用，并在体外抑制 DNA-TLR9 相互作用。

E6446 inhibits Toll-like receptor (TLR)7 and 9 signaling. E6446 works in a variety of human and mouse cell types and inhibits DNA-TLR9 interaction in vitro. When administered to mice, this compound suppress responses to challenge doses of cytidine-phosphate-guanidine (CpG)-containing DNA, which stimulates TLR9.

E6446 is a potent and orally acitve TLR7 and TLR9 inhibitor. E6446 potently suppresses DNA stimulation of HEK:TLR9 cells, with an IC50 value of 10 nM, but is significantly less effective at suppressing LPS endotoxin stimulation of HEK:TLR4 cells or R848 stimulation of HEK:TLR7 cells. E6446 potently inhibits IL-6 production induced by CpG2216 but is ineffective against induction by the TLR3 ligand poly inosine-cytosine. The ability of E6446 to inhibit TLR7 is ligand dependent, E6446 is a potent inhibitor of IL-6 induction by RNA but a relatively poor inhibitor of IL-6 induction by the small molecule imidazoquinoline ligand R-848. E6446 suppress TLR9-DNA interaction in vitro, with an IC50 in the 1 to 10 μM range. E6446 (0.01-0.03 μM) specifically inhibits TLR9 activation with CpG ODN 2006, and blocks TLR7/8 activated by the imidazoquinoline compound R848 at 2-8 μM. 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.

E6446 (20 mg/kg, p.o.) almost cmlpletely inhibits CpG1668-induced IL-6 production, and dose-dependently suppresses the development of ANA (anti-nuclear antibodies) in mice at 20 and 60 mg/kg. E6446 (20, 60 mg/kg, p.o.) dose-dependently inhibits TLR9 signaling in mice. E6446 (60, 120 mg/kg, p.o.) prevents hyperresponsiveness of TLRs and LPS-induced septic shock in rodent malaria, diminishes TLR responsiveness during acute malaria, suppresses activation of both TLR7 and TLR9.

E6446 | E 6446 | E-6446

GPCR/G Protein

Dopamine Receptor

TLR7| TLR9

Inflammation/Immunology

——

1219925-73-1

449.6

C27H35N3O3

>98% (HPLC)

——

C1CCN(C1)CCCOc1ccc(cc1)c1nc2c(o1)cc(cc2)OCCCN1CCCC1

6-(3-Pyrrolidin-1-yl-propoxy)-2-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-benzooxazole

(-20℃)

With Ice Pack

≥ 2 years