5.09225

IFN-α Receptor 2 Agonist, RO8191

• Synonyme(s) : IFN-α Receptor 2 Agonist, RO8191, 2-(2,4- bis(Trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl)-1,3,4-oxadiazole, 8-(1,3,4-Oxadiazol-2-yl)-2,4- bis(trifluoromethyl)imidazo[1, 2-a][1, 8]naphthyridine, IFN-α R2 Agonist, Interferon-α Receptor 2 Agonist, IFN-α
• Formule empirique (notation de Hill): C₁₄H₅F₆N₅O
• Poids moléculaire : 373.21
• Code UNSPSC : 12352101

Propriétés

• Essai: ≥97% (HPLC)
• Niveau de qualité: 200
• Forme: powder
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: pale yellow
• Solubilité: DMSO: 2.5 mg/mL
• Température de stockage: 2-8°C

Description

Description générale

A non-cytotoxic (up to 10 µM and 7 d in human hepatocyte Huh-7-derived HCV replicon cultures) imidazonaphthyridine compound that directly binds to the extracelluar domain of interferon-α receptor 2 (IFNAR2) in a 1:1 stoichiometric ratio and activates cellular signaling events in a IFNAR2-dependent and IFNAR1-independent manner distinct from that of interferon-α, which stimulates cellular responses only via IFNAR1/2 heterodimerization. Cellular stimulation by RO8191 via IFNAR2 homodimerization elicits similar, but not identical, signaling events as those seen with IFN-α, IFN-β, or IFN-γ stimulation. While being a much stronger stimulator of STAT3 Y705/S727 & JAK1 Y1022/1023 phosphorylations, RO8191 is ineffective in inducing IFNAR1-dependent Tyk2 Y1054/1055 phosphorylations (1 & 10 µM; 15 min; in Huh-7 cultures). Effectively boosts host anti-HCV (EC₅₀ = 200 nM in Huh-7-derived HCV replicon cell line) and anti-EMCV activity (90% vs. <3% viability with or without 1.23 µM RO8191 in EMCV-infected human A549 lung carcinoma cultures) by inducing ISG/IFN-stimulated genes expression both in cultures in vitro and in mice (30 mg/kg p.o.) in vivo and is efficacious in reducing serum HCV titre when administered to HCV-infected mice harboring humanized liver (30 mg/kg p.o.).

A non-cytotoxic compound that directly binds to the extracellular domain of interferon-α receptor 2 and activates signaling via receptor homodimerization.

A non-cytotoxic imidazonaphthyridine compound that directly binds interferon-α receptor 2 (IFNAR2) extracelluar domain in a 1:1 ratio and activates cellular signaling via IFNAR2 homodimerization in an IFNAR1-independent manner, eliciting similar, but not identical, signaling events as those seen with IFN--α, IFN--β, or IFN--γ stimulation. While being a much stronger stimulant of STAT3 Y705/S727 & JAK1 Y1022/1023 phosphorylations, RO8191 is ineffective in inducing IFNAR1-dependent Tyk2 Y1054/1055 phosphorylations (10 µM for 15 min; in Huh-7 cultures). Effectively boosts host anti-HCV (EC₅₀ = 200 nM in Huh-7-derived HCV replicon cell line) and anti-EMCV (90% viability with 1.23 µM RO8191 in EMCV-infected A549 cultures) by inducing ISG/IFN-stimulated genes expression both in cultures in vitro and in mice (30 mg/kg p.o.) in vivo.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
interferon-α receptor 2 (IFNAR2)

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Autres remarques

Konishi, H., et al. 2012. Sci. Rep.2, 259.

Informations légales

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable