Inarigivir soproxil, formerly known as SB 9200, is a potent antiviral agent. SB 9200 is also a novel agonist of innate immunity, which shows potent antiviral activity against resistant HCV variants. SB 9200 has broad-spectrum antiviral activity against RNA viruses including hepatitis C virus (HCV), norovirus, respiratory syncytial virus, and influenza and has demonstrated activity against hepatitis B virus (HBV) in vitro and in vivo. In phase I clinical trials in chronically infected HCV patients, SB 9200 has been shown to reduce HCV RNA by up to 1.9 log10 .

Physicochemical Properties

Molecular Formula	C26H38N7O12PS
Molecular Weight	703.6608
Exact Mass	703.167
Elemental Analysis	C, 44.38; H, 5.44; N, 13.93; O, 27.28; P, 4.40; S, 4.56
CAS #	942123-43-5
Related CAS #	942123-43-5 (soproxil);475650-36-3 (free);2172788-92-8 (ammonium);
PubChem CID	24737742
Appearance	White to off-white solid powder
Density	1.8±0.1 g/cm3
Index of Refraction	1.732
LogP	-0.66
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	18
Rotatable Bond Count	15
Heavy Atom Count	47
Complexity	1220
Defined Atom Stereocenter Count	7
SMILES	O([C@@H]1[C@H](OP(=O)(SCOC(=O)OC(C)C)OC[C@@H]2[C@@H](O)C[C@H](N3C=NC4C(=NC=NC3=4)N)O2)[C@@H](CO)O[C@H]1N1C=CC(=O)NC1=O)C
InChi Key	VINVIVOICCZWKJSHV-OLTNJDQQSA-N
InChi Code	InChI=1S/C26H38N7O12PS/c1-5-15-20(21(39-4)24(44-15)32-7-6-17(35)31-25(32)36)45-46(38,47-12-40-26(37)42-13(2)3)41-9-16-14(34)8-18(43-16)33-11-30-19-22(27)28-10-29-23(19)33/h10-11,13-16,18,20-21,24,34H,5-9,12H2,1-4H3,(H2,27,28,29)(H,31,35,36)/t14-,15+,16-,18-,20+,21+,24+,46?/m0/s1
Chemical Name	(((((2S,3S,5S)-5-(6-amino-9H-purin-9-yl)-3-hydroxytetrahydrofuran-2-yl)methoxy)(((2R,3R,4R,5R)-5-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-2-ethyl-4-methoxytetrahydrofuran-3-yl)oxy)phosphoryl)thio)methyl isopropyl carbonate
Synonyms	Inarigivir soproxil; SB 44 (dinucleotide); SB 9200; SB-9200; SB9200.
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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). 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

ln Vitro	First-in-class oral innate immune modulator inarigivir soproxil (SB 9200) works by stimulating the RIG-I and NOD2 pathways [1]. A strong inhibitor of HCV replication in cell culture is inarigivir soproxil. In repeat studies with four medication concentrations, the antiviral efficacy of inarigivir soproxil against HCV was assessed using the genotype 1 HCV replicon system. With EC50s of 2.2 and 1.0 µM and EC90s of 8.0 and 6.0 µM for genotypes 1A and 1B, respectively, inarigivir soproxil suppresses HCV replication [1]. An oral bioavailable dinucleotide called inarigivir soproxil (SB 9200) stimulates the interferon (IFN) signaling cascade of antiviral defense by activating viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I), and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) [2].
ln Vivo	Pretreatment with Inarigivir soproxil (SB 9200) and later entecavir (ETV) causes a host immune response, and its antiviral efficacy is superior than the method of utilizing ETV to minimize post-viral immune regulation [2]. Sequential treatment of chronic WHV carrier woodchucks with Inarigivir soproxil (30 mg/kg) followed by ETV elicited considerable decrease of serum viremia and antigenemia compared with sequential therapy with ETV followed by Inarigivir soproxil , and delay the resumption of viral replication [2].
Animal Protocol	Animal/Disease Models: woodchucks chronically infected with woodchuck hepatitis virus (WHV) [2] Doses: 30 mg/kg Route of Administration: Orally, one time/day; Group 1 received ETV treatment for 4 weeks, followed by Inarigivir soproxil treatment 12 weeks. Group 2 received Inarigivir soproxil for 12 weeks, followed by ETV for 4 weeks. Experimental Results: The liver WHV nucleic acid levels of patients in both groups were Dramatically diminished, and Group 2 was more obvious.
References	[1]. SB 9200, a novel agonist of innate immunity, shows potent antiviral activity against resistant HCV variants. J Med Virol. 2017 Sep;89(9):1620-1628. [2]. Antiviral Efficacy and Host Immune Response Induction during Sequential Treatment with SB 9200 Followed by Entecavir in Woodchucks. PLoS One. 2017 Jan 5;12(1):e0169631.
Additional Infomation	Inarigivir soproxil is under investigation in clinical trial NCT03434353 (Study to Evaluate the Antiviral Activity of Inarigivir (GS-9992) Plus Tenofovir Alafenamide (TAF) for 12 Weeks in Adults With Chronic Hepatitis B (CHB)).

Solubility Data

Solubility (In Vitro)

DMSO : ~80 mg/mL (~113.70 mM) H2O : ~10 mg/mL (~14.21 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (7.11 mM) 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 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 4 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 40.0 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 3: ≥ 4 mg/mL (5.68 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 40.0 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 4: ≥ 2.5 mg/mL (3.55 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: (saturation unknown) in 10% DMSO+90% Corn Oil: ≥ 5 mg/mL (7.11 mM) (add these co-solvents sequentially from left to right, and one by one), Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.4211 mL	7.1057 mL	14.2114 mL
	5 mM	0.2842 mL	1.4211 mL	2.8423 mL
	10 mM	0.1421 mL	0.7106 mL	1.4211 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.