Enpatoran hydrochloride (M5049 hydrochloride) is an orally active, selective, and potent TLR7/8 inhibitor with antiviral activity for the study of autoimmune diseases and COVID-19 pneumonia.

TLR8:24.1 nM (IC50), TLR7:11.1 nM (IC50)

0.01 nM-10 μM Enpatoran hydrochloride, was able to inhibit IL-6 production induced by all ligands (e.g., miR-122, Let7c RNA, Alu RNA, and R848) with IC50 values ranging from 35 to 45 nM. [1]

Injection of R848 (25 μg intraperitoneally) into mice was able to dose-dependently inhibit IL-6 and IFN-α production after pretreatment with 1 mg/kg Enpatoran hydrochloride by oral gavage.
Enpatoran hydrochloride exhibited good bioavailability after oral administration of 1.0 mg/kg (100% in mice, 87% in rats, and 84% in dogs). Following intravenous administration, Enpatoran hydrochloride has a moderate half-life (1.4 hours in mice, 5.0 hours in rats, and 13 hours in dogs), which is associated with its high plasma clearance (1.4 L/h/kg in mice, 1.2 L/h/kg in rats, and 0.59 L/h/kg in dogs, respectively) and large volume of distribution (2.7 L/kg in mice, 8.7 L/kg in rats, and 8.7 L/kg in dogs, respectively). /in mice, 8.7 L/kg in rats, and 5.7 L/kg in dogs, respectively). [1]