RO8191 (RO-8191; CDM-3008) is a novel and potent activator of JAK/STAT pathway and interferon α receptor type 2 (IFNAR2) with antiviral effects. It is effective against HCV with EC50 value of 200 nM. RO8191 phosphorylates STAT1 and STAT2, which functions as a gateway to the type I IFN signal cascade, and stimulates the phosphorylation of STAT3, 5 and 6.

Physicochemical Properties

Molecular Formula	C14H5F6N5O
Molecular Weight	373.212822675705
Exact Mass	373.039
CAS #	691868-88-9
PubChem CID	2768133
Appearance	Off-white to yellow solid powder
LogP	3.7
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	1
Heavy Atom Count	26
Complexity	531
Defined Atom Stereocenter Count	0
SMILES	FC(C1C=C(C(F)(F)F)N=C2C=1C=CC1=NC(C3=NN=CO3)=CN21)(F)F
InChi Key	GRHYZVJEXKTJOS-UHFFFAOYSA-N
InChi Code	InChI=1S/C14H5F6N5O/c15-13(16,17)7-3-9(14(18,19)20)23-11-6(7)1-2-10-22-8(4-25(10)11)12-24-21-5-26-12/h1-5H
Chemical Name	2-[2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole
Synonyms	RO8191 CDM-3008 RO 8191 CDM3008 RO-8191
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	JAK1; IFNAR2
ln Vitro	CDM-3008, also known as RO8191, exhibits antiviral activity that is reliant on IFNAR2/JAK1 but not IFNAR1/Tyk2. IFNAR2 agonist RO8191 is known to activate IFN signaling in mice [1]. HCV replicon activity was significantly suppressed by RO8191 (0.08, 0.4, 2, 10 μM; for 72 hours) in a dose-dependent way. The HCV NS3 and NS4A protein levels are mostly decreased by RO8191 in the replicon cells' perinuclear area [1]. Viral proteins including NS3, NS4A/B, and NS5A/B vanish when exposed to RO8191 (0.08–10 μM) over 72 hours [1].
ln Vivo	In the liver of 6-week-old C57BL/6J mice, RO8191 (CDM-3008; 30 mg/kg; oral) dramatically increased the expression of the antiviral genes Oas1b, Mx1, and Pkr [1].
References	[1]. An Orally Available, Small-Molecule Interferon Inhibits Viral Replication. Sci Rep. 2012;2:259. [2]. An interferon-like small chemical compound CDM-3008 suppresses hepatitis B virus through induction of interferon-stimulated genes. PLoS One. 2019 Jun 12;14(6):e0216139.

Solubility Data

Solubility (In Vitro)

DMSO : ~5 mg/mL (~13.40 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 0.5 mg/mL (1.34 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 0.5 mg/mL (1.34 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 0.5 mg/mL (1.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6795 mL	13.3973 mL	26.7946 mL
	5 mM	0.5359 mL	2.6795 mL	5.3589 mL
	10 mM	0.2679 mL	1.3397 mL	2.6795 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.