Enpatoran hydrochloride (C09-1130-948)

Enpatoran (M5049) hydrochloride is a potent, orally active and dual TLR7/8 inhibitor with IC 50 s of 11.1 nM and 24.1 nM in HEK293 cells, respectively. Enpatoran hydrochloride is inactive against TLR3 , TLR4 and TLR9 . Enpatoran hydrochloride can block molecule synthetic ligands and natural endogenous RNA ligands. Enpatoran hydrochloride exhibits excellent pharmacokinetic properties in vivo . Enpatoran hydrochloride can be used for both innate and adaptive autoimmunity blocking researchIn VitroEnpatoran hydrochloride (0.01 nM-10 μM) inhibits production of IL-6 stimulated by all the ligands (miR-122, Let7c RNA, Alu RNA, and R848) with IC 50 values ranging from 35 to 45 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoPre-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 . Enpatoran hydrochloride exhibits high oral bioavailability (mouse 100%, rat 87%, dog 84%) following oral administration (mouse, rat and dog 1.0 mg/kg) . Enpatoran hydrochloride exhibits moderate half-lives (mouse 1.4, rat 5.0 and dog 13 h) due to high plasma clearance (1.4, 1.2 and 0.59 L/h/kg, respectively) combined with large volumes of distribution (2.7, 8.7 and 5.7 L/kg, respectively) following intravenous administration (mouse, rat and dog 1.0 mg/kg) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female C57BL/6 mice Dosage: 0.1 mg/kg and 1 mg/kg Administration: Oral gavage; administered 1 hour prior to R848 challenge Result: The TLR7/8 agonist R848 stimulated both IFN-α and IL-6 production in mice. Enpatoran hydrochloride decreased IFN-α and IL-6 production stimulated by R848.Form:SolidIC50& Target:TLR7 11.1 nM (IC 50 ) TLR8 24.1 nM (IC 50 ). Specifications and Purity: 98%. Molecular Formula: C16H16ClF3N4. Molecular Weight: 356.77.