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Purity: ≥98%
Inarigivir (formerly also known as ORI-9020; SB-9000) is a novel and potent dinucleotide which can significantly reduce liver HBV DNA in transgenic mice expressing hepatitis B virus. It was evaluated in transgenic mice expressing hepatitis B virus (HBV), significantly reduced liver HBV DNA (P
| Targets |
ORI-9020 is a novel phosphorothioate dinucleotide. Its proposed mode of antiviral action is direct interference with hepatitis B virus (HBV) replication at the level of the HBV reverse transcriptase and/or DNA polymerase, at an early step (at or prior to the production of the first strand of HBV DNA). (No specific IC50, Ki, or EC50 values for enzyme inhibition are provided in this article.) [1]
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| ln Vitro |
The nucleos(t)ide analogs authorized for the treatment of chronic hepatitis B are all susceptible to resistance markers when it comes to HBV variations that are active against inarigivir (SB 9200) [2].
Inarigivir showed antiviral activity against a panel of nucleos(t)ide analogue-resistant HBV variants (rtL180M/rtM204V, rtM204I, rtA181V/rtN236T, and rtL180M/rtT184G/rtS202I/rtM204V) in transiently transfected Huh7 cells. Dose-dependent inhibition of HBV DNA replicative intermediate single strand (SS) was observed, with inhibition exceeding 20% compared to untreated controls. [2] Inarigivir also exhibited antiviral activity against HBV core protein assembly modifier (CpAM)-resistant variants (cT33I, cY109A, cT118F, cV124A, cY132A) and the precore stop codon variant G1896A in Huh7 cells. All tested variants remained sensitive to Inarigivir treatment. [2] |
| ln Vivo |
Inarigivir (100 mg/kg/day, i.p.) shown anti-HBV efficacy and markedly decreased the amount of viral DNA in the liver. Treatment has no effect on the level of serum HBV DNA. Serum HBeAg levels, mean HBsAg titers, and liver HBV RNA levels were all unaffected by inarigivir. Based on liver HBV DNA levels, the lowest effective dose is 1.6 to 0.5 mg/kg/day [1].
In a transgenic mouse model expressing HBV, intraperitoneal (i.p.) administration of ORI-9020 at 100 mg/kg/day for 14 days significantly reduced viral DNA in the liver (P ≤ 0.001) compared to vehicle controls. This anti-HBV activity was similar to that of the positive control, adefovir dipivoxil (10 mg/kg/day). [1] Treatment with ORI-9020 did not significantly reduce serum HBV DNA levels, liver HBV RNA levels, serum HBeAg, serum HBsAg, or liver HBeAg levels. [1] The minimal effective dosage of ORI-9020 administered i.p. was determined to be between 1.6 and 0.5 mg/kg/day, based on the reduction of HBV DNA in the liver. This activity range was similar to the previously determined minimal effective oral dose of adefovir dipivoxil (1.0 - 0.3 mg/kg/day) in the same model. [1] |
| Cell Assay |
Huh7 cells were transiently transfected with replication-competent HBV clones carrying resistance mutations to nucleos(t)ide analogues or core protein substitutions. Cells were treated with Inarigivir at concentrations of 50, 25, and 2.0 µM for 5 days. After treatment, cells were harvested, core preparations were made, DNA was extracted, and Southern blot analysis was performed to detect HBV DNA replicative intermediates. Antiviral activity was scored as sensitive if a dose-response was observed and inhibition exceeded 20% compared to untreated controls. [2]
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| Animal Protocol |
Animal/Disease Models: Mice[1]
Doses: 100 mg/kg. Management: IP, daily. Experimental Results: Viral DNA was Dramatically diminished in the liver and demonstrated anti-HBV activity similar to the ADV positive control. Experiment 1 (Efficacy): Male transgenic HBV mice were block-randomized based on serum HBeAg titers. ORI-9020 was prepared fresh daily at a dose of 100 mg/kg/day and administered by intraperitoneal (i.p.) injection once daily for 14 days. The drug was formulated in either a cremaphor-ethanol-saline (CES) vehicle (10:10:80) or physiological saline. Adefovir dipivoxil (10 mg/kg/day in CES) and vehicle-only groups served as controls. Necropsy was performed at least 2 hours after the last dose to collect liver and serum samples. [1] Experiment 2 (Minimal Effective Dose): Female transgenic HBV mice received i.p. injections of ORI-9020 prepared in sterile saline at one-half-log serial dilutions ranging from 50 to 0.05 mg/kg/day. The injection volume was 0.1 ml. Animals were treated once daily, and necropsy was performed as in Experiment 1. Liver HBV DNA levels were used to determine the minimal effective dose. [1] |
| Toxicity/Toxicokinetics |
In the transgenic mouse study, researchers monitored the mice's weight gain and survival rate. [1]
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| References |
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| Additional Infomation |
Inarigivir is being investigated in the clinical trial NCT03434353 (a study evaluating the antiviral activity of inarigivir (GS-9992) in combination with tenofovir alafenamide (TAF) for 12 weeks in adult patients with chronic hepatitis B (CHB). ORI-9020 is a novel phosphate-thioester dinucleotide. [1] Southern blot analysis showed that ORI-9020 treatment appeared to indiscriminately reduce all types of HBV DNA in the liver, unlike adefovir dipivoxil, which typically leaves low molecular weight viral DNA bands. This suggests that its mechanism of action in reducing viral DNA in the liver may be different. [1] The study concluded that intraperitoneal injection of ORI-9020 had similar anti-HBV activity in this transgenic mouse model as oral adefovir dipivoxil. [1]
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| Molecular Formula |
C20H26N7O10PS
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| Molecular Weight |
587.500103473663
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| Exact Mass |
587.119
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| CAS # |
475650-36-3
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| Related CAS # |
Inarigivir ammonium;2172788-92-8
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| PubChem CID |
6912016
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| Appearance |
White to off-white solid powder
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| LogP |
-1.8
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
39
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| Complexity |
1010
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| Defined Atom Stereocenter Count |
7
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| SMILES |
S=P(O)(OCC1C(CC(N2C=NC3C(N)=NC=NC2=3)O1)O)OC1C(CO)OC(C1OC)N1C=CC(NC1=O)=O
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| InChi Key |
LYMICVBGNUEHGE-FUQPUAIBSA-N
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| InChi Code |
InChI=1S/C20H26N7O10PS/c1-33-16-15(10(5-28)36-19(16)26-3-2-12(30)25-20(26)31)37-38(32,39)34-6-11-9(29)4-13(35-11)27-8-24-14-17(21)22-7-23-18(14)27/h2-3,7-11,13,15-16,19,28-29H,4-6H2,1H3,(H,32,39)(H2,21,22,23)(H,25,30,31)/t9-,10+,11+,13+,15+,16+,19+,38?/m0/s1
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| Chemical Name |
O-(((2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-3-hydroxytetrahydrofuran-2-yl)methyl) O-((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-(hydroxymethyl)-4-methoxytetrahydrofuran-3-yl) S-hydrogen phosphorothioate
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| Synonyms |
Inarigivir soproxil; ORI-9020; ORI 9020; ORI9020; SB-40; SB-9000; SB9000, SB-9000.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~340.43 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.26 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 2: ≥ 2.5 mg/mL (4.26 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. View More
Solubility in Formulation 3: ≥ 0.25 mg/mL (0.43 mM) (saturation unknown) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7021 mL | 8.5106 mL | 17.0213 mL | |
| 5 mM | 0.3404 mL | 1.7021 mL | 3.4043 mL | |
| 10 mM | 0.1702 mL | 0.8511 mL | 1.7021 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Southern blot hybridization for HBV DNA in the livers of mice treated i.p. with ORI-9020, ADV, or vehicle only.Antimicrob Agents Chemother. 2004 Jun; 48(6): 2318–2320. |
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 Determination of minimal effective concentration of ORI-9020 using liver HBV DNA parameter in transgenic mice.Antimicrob Agents Chemother. 2004 Jun; 48(6): 2318–2320. |
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