e6446-hcl

Description: E6446 is a synthetic antagonist of nucleic acid-sensing TLRs. , In vitro, low doses of E6446 specifically inhibited the activation of human and mouse TLR9. Tenfold higher concentrations of this compound also inhibited the human TLR8 response to single-stranded RNA. In vivo, therapy with E6446 diminished the activation of TLR9 and prevented the exacerbated cytokine response observed during acute Plasmodium infection. Furthermore, severe signs of ECM, such as limb paralysis, brain vascular leak, and death, were all prevented by orally bioavailable treatment with E6446.

References: Franklin BS, Ishizaka ST, Lamphier M, Gusovsky F, Hansen H, Rose J, Zheng W, Ataide MA, de Oliveira RB, Golenbock DT, Gazzinelli RT. Therapeutical targetingof nucleic acid-sensing Toll-like receptors prevents experimental cerebralmalaria. Proc Natl Acad Sci U S A. 2011 Mar 1; 108(9):3689-94. doi:10.1073/pnas.1015406108. Epub 2011 Feb 8. PubMed PMID: 21303985; PubMed CentralPMCID: PMC3048158.