Inarigivir (ORI-9020)
(Synonyms: ORI-9020; SB-9000) 目录号 : GC32104
Inarigivir (ORI-9020) (ORI-9020) 是一种二核苷酸抗病毒药物，可显着降低表达乙型肝炎病毒的转基因小鼠的肝脏 HBV DNA。
Cas No.:475650-36-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mice[1]For the first animal experiment, Inarigivir is prepared fresh daily at a dosage of 100 mg/kg of body weight /day, which is equal to 170 mol/kg/day, and is injected intraperitoneally (i.p.) using cremaphor-ethanol-saline (CES) (10:10:80) or physiological saline as vehicles. ADV, the positive control, is prepared using the CES vehicle. A dosage of 10 mg/kg/day (19.9 mol/kg/day) is used. In the second experiment to determine the minimal effective concentration, Inarigivir is prepared in sterile saline in onehalf-log dilutions from 50 to 0.05 mg/kg/day. The drug is delivered i.p. in a volume of 0.1 ml. Liver samples are analyzed for HBV DNA, HBV RNA, and HBcAg, and serum samples are processed for HBV DNA, HBeAg, and HBsAg[1]. |
References: [1]. Iyer RP, et al. Anti-hepatitis B virus activity of ORI-9020, a novel phosphorothioate dinucleotide, in a transgenic mouse model. Antimicrob Agents Chemother. 2004 Jun;48(6):2318-20. | |
Inarigivir (ORI-9020;SB-9000) is a dinucleotide which can significantly reduce liver HBV DNA in transgenic mice expressing hepatitis B virus.
I.p. injection of Inarigivir at 100 mg/kg/day significantly reduces viral DNA in the liver and shows anti-HBV activity similar ADV positive control. Serum HBV DNA is not reduced in response to treatment. Inarigivir does not affect levels of HBV RNA in liver, levels of HBeAg in serum, or mean titers of HBsAg. The minimal effective dose is identified to be between 1.6 and 0.5 mg/kg/day using liver HBV DNA values[1].
[1]. Iyer RP, et al. Anti-hepatitis B virus activity of ORI-9020, a novel phosphorothioate dinucleotide, in a transgenic mouse model. Antimicrob Agents Chemother. 2004 Jun;48(6):2318-20.
| Cas No. | 475650-36-3 | SDF | |
| 别名 | ORI-9020; SB-9000 | ||
| Canonical SMILES | NC1=C(N=CN2[C@@H]3O[C@H](COP(O[C@H]4[C@@H](OC)[C@H](N5C=CC(NC5=O)=O)O[C@@H]4CO)(S)=O)[C@@H](O)C3)C2=NC=N1 | ||
| 分子式 | C20H26N7O10PS | 分子量 | 587.5 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
NOD2/RIG-I Activating Inarigivir Adjuvant Enhances the Efficacy of BCG Vaccine Against Tuberculosis in Mice
Front Immunol 2020 Dec 7;11:592333.PMID:33365029DOI:10.3389/fimmu.2020.592333.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) kills about 1.5 million people each year and the widely used Bacille Calmette-Guérin (BCG) vaccine provides a partial protection against TB in children and adults. Because BCG vaccine evades lysosomal fusion in antigen presenting cells (APCs), leading to an inefficient production of peptides and antigen presentation required to activate CD4 T cells, we sought to boost its efficacy using novel agonists of RIG-I and NOD2 as adjuvants. We recently reported that the dinucleotide SB 9200 (Inarigivir) derived from our small molecule nucleic acid hybrid (SMNH)® platform, activated RIG-I and NOD2 receptors and exhibited a broad-spectrum antiviral activity against hepatitis B and C, Norovirus, RSV, influenza and parainfluenza. Inarigivir increased the ability of BCG-infected mouse APCs to secrete elevated levels of IL-12, TNF-α, and IFN-β, and Caspase-1 dependent IL-1β cytokine. Inarigivir also increased the ability of macrophages to kill MTB in a Caspase-1-, and autophagy-dependent manner. Furthermore, Inarigivir led to a Capsase-1 and NOD2- dependent increase in the ability of BCG-infected APCs to present an Ag85B-p25 epitope to CD4 T cells in vitro. Consistent with an increase in immunogenicity of adjuvant treated APCs, the Inarigivir-BCG vaccine combination induced robust protection against tuberculosis in a mouse model of MTB infection, decreasing the lung burden of MTB by 1-log10 more than that afforded by BCG vaccine alone. The Inarigivir-BCG combination was also more efficacious than a muramyl-dipeptide-BCG vaccine combination against tuberculosis in mice, generating better memory T cell responses supporting its novel adjuvant potential for the BCG vaccine.
Review article: clinical pharmacology of current and investigational hepatitis B virus therapies
Aliment Pharmacol Ther 2020 Jan;51(2):231-243.PMID:31840863DOI:10.1111/apt.15581.
Background: Treatment of hepatitis B virus (HBV) infection with current therapy suppresses HBV DNA, but loss of hepatitis B surface antigen (HBsAg; functional cure), is rare. Multiple compounds are under investigation. Aims: To describe the pharmacology, including drug interactions, efficacy, safety and mechanisms of action of investigational compounds for HBV infection. Methods: Descriptive review using PubMed and Google to identify literature/conference papers on investigational compounds (≥Phase 2) with data on efficacy and safety in HBV-infected patients. Results: Bulevirtide, JNJ-56136379, ABI-H0731, REP-2139, and Inarigivir decrease HBV DNA/RNA, with greater potency than current nucleos(t)ide analogues. REP-2139 (25%-75% of patients, 20-48 weeks treatment) and Inarigivir (26% of patients, 12-24 weeks treatment) induce HBsAg loss. ARO-HBV reduced (>1.5 log10 UI/mL) HBsAg in 85% of patients (12 weeks treatment). There are some safety concerns with investigational agents (e.g., increased bile acids with bulevirtide, and liver enzyme flares with REP-2139) which will require a risk benefit assessment compared with current therapies. Single and multidose pharmacokinetic data are available for bulevirtide, JNJ-56136379, ABI-H0731; no such data are available for REP-2139, ARO-HBV, Inarigivir. Initial drug interaction assessments have been performed with bulevirtide and Inarigivir (only in vitro). Conclusions: There are promising investigational therapies for HBV infection. Increasing the potential for HBsAg loss may result in more patients achieving functional cure. However, many knowledge gaps remain such as pharmacokinetics in those with HBV, cirrhosis and renal impairment but also the interaction potential between investigational therapies, risk-benefit profiles, and potential for drug interactions with medications used to treat comorbidities associated with aging.
A phase 2, open-label, randomized, multiple-dose study evaluating Inarigivir in treatment-naïve patients with chronic hepatitis B
Liver Int 2023 Jan;43(1):77-89.PMID:36300646DOI:10.1111/liv.15465.
Background/aims: Novel agents acting against hepatitis B virus (HBV) are needed to improve HBsAg seroclearance or termed as 'functional cure'. Inarigivir (retinoic acid-inducible gene I agonist) has immunomodulatory and direct antiviral actions against HBV. We aimed to determine the safety and efficacy of Inarigivir for the treatment of HBV infection. Patients/methods: 80 treatment-naïve patients were randomized in 4 ascending dose cohorts to receive 12 weeks of Inarigivir 25, 50, 100, 200 mg or placebo in a ratio of 4:1. All patients were then given tenofovir for another 12 weeks. Results: Least squares (LS) mean reductions in HBV DNA from baseline increased with higher doses of Inarigivir (0.6116 in 25 mg and 1.5774 in 200 mg groups vs. 0.0352 in placebo group) (95% CI 0.9518-0.2011 and 1.921-1.1634 respectively). LS mean changes in HBV RNA and HBsAg from baseline ranged from -0.3856 to -0.5794 versus -0.1474 and -0.0956 to -0.1818 versus +0.0026 in Inarigivir-treated versus placebo groups respectively. During the tenofovir-treated period, LS mean reductions in HBsAg in the Inarigivir-treated groups ranged from 0.1709 to 0.3529 versus 0.1984 in the placebo group. Inarigivir-treated groups showed mean reductions in ALT from baseline between 23.3 and 33.8 versus 0.7 U/L in the placebo group. Treatment-emergent adverse events related to Inarigivir and placebo occurred in 4.7% and 6.3% patients respectively. Conclusions: Twelve-week Inarigivir up to 200 mg dose was associated with a reduction of HBV DNA, HBV RNA and antigen levels. A trend for greater HBsAg reduction was observed in Inarigivir pre-treated patients after switching to tenofovir.