E6446

**E6446** is an orally active small molecule antagonist primarily targeting Toll-like receptors (TLRs) 7 and 9, inhibiting their activation by nucleic acids such as DNA and RNA. Developed by **Eisai**, it potently blocks TLR9 signaling (IC50 = 0.01 μM) and TLR7 signaling (IC50 = 1.78 μM), with selectivity over TLR4 (IC50 > 30 μM), preventing proinflammatory cytokine release in various human and mouse cell types. It has demonstrated protective effects in preclinical models of cerebral malaria by suppressing TLR9-mediated hyperinflammation and vascular pathology, as well as emerging evidence of SCD1 inhibition reducing adipogenesis and hepatic lipogenesis in nonalcoholic fatty liver disease (NAFLD) models via SCD1-ATF3 signaling (KD = 4.61 μM).[1][3][5][7][2]