| Identification | Back Directory | [Name]
8-Quinolinecarbonitrile, 5-[(3R,5S)-3-amino-5-(trifluoromethyl)-1-piperidinyl]-, hydrochloride (1:1) | [CAS]
2101945-93-9 | [Synonyms]
8-Quinolinecarbonitrile, 5-[(3R,5S)-3-amino-5-(trifluoromethyl)-1-piperidinyl]-, hydrochloride (1:1) | [Molecular Formula]
C16H16ClF3N4 | [MOL File]
2101945-93-9.mol | [Molecular Weight]
356.78 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C, sealed storage, away from moisture and light | [solubility ]
DMSO : 16.67 mg/mL (46.72 mM; ultrasonic and warming and heat to 60°C) | [form ]
Solid | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
Enpatoran (M5049) hydrochloride is a potent, orally active and dual TLR7/8 inhibitor with IC50s 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 research[1]. | [Biological Activity]
Enpatoran (M5049) hydrochloride is a potent, orally active and dual TLR7/8 inhibitor with IC50s 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 research[1].
Enpatoran 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 IC50 values ranging from 35 to 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 exhibits high oral bioavailability (mouse 100%, rat 87%, dog 84%) following oral administration (mouse, rat and dog 1.0 mg/kg)[1]. 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)[1]. | [in vivo]
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 exhibits high oral bioavailability (mouse 100%, rat 87%, dog 84%) following oral administration (mouse, rat and dog 1.0 mg/kg)[1].
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)[1]. | Animal Model: | Female C57BL/6 mice[1] | | 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. |
| [IC 50]
TLR7: 11.1 nM (IC50); TLR8: 24.1 nM (IC50) | [storage]
Store at -20°C, sealed storage, away from moisture and light | [References]
[1]. Jaromir Vlach, et al. Discovery of M5049: A Novel Selective TLR7/8 Inhibitor for Treatment of Autoimmunity. J Pharmacol Exp Ther. 2020 Dec 16;JPET-AR-2020-000275. |
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