Enpatoran (M5049) hydrochloride is a potent, orally active dual inhibitor of TLR7/8 with IC50 values of 11.1 nM and 24.1 nM in HEK293 cells, respectively. This compound specifically inhibits TLR7 and TLR8 without affecting TLR3, TLR4, or TLR9, and blocks both synthetic molecule ligands and natural endogenous RNA ligands. Enpatoran hydrochloride also exhibits excellent pharmacokinetic properties in vivo, making it a valuable tool for studying and modulating innate and adaptive autoimmunity. [1]

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

Enpatoran hydrochloride (0.01 nM-10 μM) inhibits IL-6 production stimulated by miR-122, Let7c RNA, Alu RNA, and R848, with IC50 values between 35 and 45 nM[1].

Pre-treatment with Enpatoran hydrochloride (oral gavage; 1 mg/kg) before R848 (intraperitoneal injection of 25 μg) dose-dependently inhibits the production of IL-6 and IFN-α in mice[1]. Enpatoran hydrochloride shows high oral bioavailability (mouse 100%, rat 87%, dog 84%) following oral administration (1.0 mg/kg)[1]. It exhibits moderate half-lives (mouse 1.4 h, rat 5.0 h, dog 13 h) due to high plasma clearance (1.4, 1.2, 0.59 L/h/kg) and large volumes of distribution (2.7, 8.7, 5.7 L/kg) following intravenous administration (1.0 mg/kg)[1].