Azvudine hydrochloride
(Synonyms: RO-0622 hydrochloride; FNC hydrochloride) 目录号 : GC60071
Azvudine hydrochloride 是一种有效的核苷逆转录酶抑制剂 (NRTI)，对 HIV、HBV 和 HCV（HIV-1（EC50 0.03 至 6.92 nM）和 HIV-2（EC50 0.018 至 0.025 nM）具有抗病毒活性。
Cas No.:1333126-31-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
C8166 cells |
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Preparation Method |
Cells were seeded each well in a 96-well plate with Azvudine hydrochloride . The plate was placed in a humidified incubator. After incubation of 3-7 days, the percentage inhibition of syncytia formation was scored or the level of p24 was measured by ELISA and 50% effective concentration (EC50) were calculated. |
|
Reaction Conditions |
2nM Azvudine hydrochloride for 3-7 days at 37°C |
|
Applications |
Azvudine hydrochloride showed strong inhibition against wild-type HIV-1 IIIB and HIV-1 RF, with 50% effective concentration values (EC 50) ranging from 30 to 110 pM. |
| Animal experiment [2]: | |
|
Animal models |
Lethal EV71 and CA16 infection in neonatal mouse models |
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Preparation Method |
The neonatal mice were randomly divided into five groups, and each group contained three litters . One group was inoculated intracerebrally with DMEM (10 µl/mouse) and after 1 h injected intraperitoneally with DMSO. Two groups were inoculated intracerebrally with EV71 CC063 and after 1 h injected intraperitoneally with Azvudine hydrochloride or DMSO. Azvudine hydrochloride was injected intraperitoneally on days 1, 3, 6, 9, and 12 |
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Dosage form |
1 mg/kg Azvudine hydrochloride on days 1, 3, 6, 9, and 12 |
|
Applications |
EV71 and CA16 challenge resulted in 90% and 30% mortality, respectively, while Azvudine hydrochloride Azvudine hydrochloride treatment greatly reduced mortality to 20% and 0%. Azvudine hydrochloride treatment significantly improved clinical presentation and survival, indicating that FNC effectively protects against EV71 and CA16 challenge in vivo. |
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References: [1]. Wang RR, Yang QH,et,al. Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. PLoS One. 2014 Aug 21;9(8):e105617. doi: 10.1371/journal.pone.0105617. PMID: 25144636; PMCID: PMC4140803. | |
Azvudine hydrochloride is a potent nucleoside reverse transcriptase inhibitor (NRTI) that has antiviral activity against HIV, HBV, and HCV,(HIV-1 (EC50s 0.03 to 6.92 nM) and HIV-2 (EC50s 0.018 to 0.025 nM))[1]. Azivudine hydrochloride could inhibit SARS-CoV-2 and HCoV-OC43 coronavirus with EC50 1.2-4.3 μM[3].
In C8166 cells,Azvudine hydrochloride showed strong inhibition against wild-type HIV-1 IIIB and HIV-1 RF, with 50% effective concentration values (EC 50) ranging from 30 to 110 pM[2].
EV71 and CA16 challenge resulted in 90% and 30% mortality, respectively, while Azvudine hydrochloride treatment greatly reduced mortality to 20% and 0%. Azvudine hydrochloride treatment significantly improved clinical presentation and survival, indicating that Azvudine hydrochloride effectively protects against EV71 and CA16 challenge in vivo[4].
Treating SARS-CoV-2 infected rhesus macaques with Azvudine hydrochloride (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray[3].
Azvudine hydrochloride clinical efficacy in curing COVID-19 was significant, showing inhibition of SARS-CoV-2 replication in all 31 patients after treatment with Azvudine hydrochloride, and the anti-coronavirus activity of Azvudine hydrochloride was also demonstrated in animal experiments using RM[5].
References:
[1]: Wang RR, Yang QH, et,al. Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. PLoS One. 2014 Aug 21;9(8):e105617. doi: 10.1371/journal.pone.0105617. PMID: 25144636; PMCID: PMC4140803.
[2]: Zhou Y, Zhang Y, et,al.Novel nucleoside analogue FNC is effective against both wild-type and lamivudine-resistant HBV clinical isolates. Antivir Ther. 2012;17(8):1593-9. doi: 10.3851/IMP2292. Epub 2012 Aug 9. PMID: 22910281.
[3]: Zhang JL, Li YH, et,al. Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients. Signal Transduct Target Ther. 2021 Dec 6;6(1):414. doi: 10.1038/s41392-021-00835-6. PMID: 34873151; PMCID: PMC8646019.
[4]: Xu N, Yang J, et,al.The Pyrimidine Analog FNC Potently Inhibits the Replication of Multiple Enteroviruses. J Virol. 2020 Apr 16;94(9):e00204-20. doi: 10.1128/JVI.00204-20. PMID: 32075935; PMCID: PMC7163137.
[5]: Ren Z, Luo H, et,al. A Randomized, Open-Label, Controlled Clinical Trial of Azvudine Tablets in the Treatment of Mild and Common COVID-19, a Pilot Study. Adv Sci (Weinh). 2020 Aug 13;7(19):2001435. doi: 10.1002/advs.202001435. PMID: 32837847; PMCID: PMC7404576.
[6]: Fayzullina D, Kharwar RK, et,al. FNC: An Advanced Anticancer Therapeutic or Just an Underdog? Front Oncol. 2022 Feb 10;12:820647. doi: 10.3389/fonc.2022.820647. PMID: 35223502; PMCID: PMC8867032.
Azvudine hydrochloride 是一种有效的核苷逆转录酶抑制剂 (NRTI)，对 HIV、HBV 和 HCV（HIV-1（EC50 0.03 至 6.92 nM）和 HIV-2（EC50 0.018 至 0.025 nM））具有抗病毒活性[1]。盐酸阿齐夫定对SARS-CoV-2和HCoV-OC43冠状病毒具有抑制作用，EC50为1.2-4.3 μM[3]。
在 C8166 细胞中，盐酸阿兹夫定对野生型 HIV-1 IIIB 和 HIV-1 RF 表现出强烈的抑制作用，50% 有效浓度值 (EC 50) 范围为 30 至 110 pM[2].
EV71 和 CA16 攻击分别导致 90% 和 30% 的死亡率，而盐酸阿兹夫定处理将死亡率大大降低至 20% 和 0%。阿兹夫定盐酸盐治疗显着改善了临床表现和生存率，表明阿兹夫定盐酸盐可有效保护体内免受 EV71 和 CA16 攻击[4]。
用盐酸阿兹夫定（0.07 毫克/千克，每日一次，口服）治疗感染 SARS-CoV-2 的恒河猴，可降低病毒载量，恢复胸腺，改善淋巴细胞分布，减轻炎症和器官损伤，并减轻毛玻璃样混浊胸部 X 光片[3].
盐酸阿兹夫定治疗 COVID-19 的临床疗效显着，在所有 31 名接受盐酸阿兹夫定治疗后的患者中均表现出抑制 SARS-CoV-2 复制的作用，并且在动物实验中也证明了盐酸阿兹夫定的抗冠状病毒活性RM[5].
| Cas No. | 1333126-31-0 | SDF | |
| 别名 | RO-0622 hydrochloride; FNC hydrochloride | ||
| Canonical SMILES | NC(C=CN1[C@@H]2O[C@@](N=[N+]=[N-])([C@H]([C@@H]2F)O)CO)=NC1=O.[H]Cl | ||
| 分子式 | C9H12ClFN6O4 | 分子量 | 322.68 |
| 溶解度 | Water: 125 mg/mL (387.38 mM) | 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.099 mL | 15.4952 mL | 30.9905 mL |
| 5 mM | 0.6198 mL | 3.099 mL | 6.1981 mL |
| 10 mM | 0.3099 mL | 1.5495 mL | 3.099 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。
Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients
Signal Transduct Target Ther2021 Dec 6;6(1):414.PMID: 34873151DOI: 10.1038/s41392-021-00835-6
Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 ¦̍, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ¡À 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ¡À 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.
Azvudine (FNC): a promising clinical candidate for COVID-19 treatment
Signal Transduct Target Ther2020 Oct 10;5(1):236.PMID: 33040075DOI: 10.1038/s41392-020-00351-z
A Randomized, Open-Label, Controlled Clinical Trial of Azvudine Tablets in the Treatment of Mild and Common COVID-19, a Pilot Study
Adv Sci (Weinh)2020 Aug 13;7(19):2001435.PMID: 32837847DOI: 10.1002/advs.202001435
Coronavirus disease 2019 (COVID-19) has spread worldwide. To date, no specific drug for COVID-19 has been developed. Thus, this randomized, open-label, controlled clinical trial (ChiCTR2000029853) was performed in China. A total of 20 mild and common COVID-19 patients were enrolled and randomly assigned to receive Azvudine and symptomatic treatment (FNC group), or standard antiviral and symptomatic treatment (control group). The mean times of the first nucleic acid negative conversion (NANC) of ten patients in the FNC group and ten patients in the control group are 2.60 (SD 0.97; range 1-4) d and 5.60 (SD 3.06; range 2-13) d, respectively (p = 0.008). The mean times of the first NANC of four newly diagnosed subjects in the FNC group and ten subjects in the control group are 2.50 (SD 1.00; range 2-4) d and 9.80 (SD 4.73; range 3-19) d, respectively (starting from the initial treatment) (p = 0.01). No adverse events occur in the FNC group, while three adverse events occur in the control group (p = 0.06). The preliminary results show that FNC treatment in the mild and common COVID-19 may shorten the NANC time versus standard antiviral treatment. Therefore, clinical trials of FNC treating COVID-19 with larger sample size are warranted.
A Randomized, Open-Label, Controlled Clinical Trial of Azvudine Tablets in the Treatment of Mild and Common COVID-19, a Pilot Study
Adv Sci (Weinh)2020 Oct;7(19):e2001435.PMID: 35403380DOI: 10.1002/advs.202001435
Coronavirus disease 2019 (COVID-19) has spread worldwide. To date, no specific drug for COVID-19 has been developed. Thus, this randomized, open-label, controlled clinical trial (ChiCTR2000029853) was performed in China. A total of 20 mild and common COVID-19 patients were enrolled and randomly assigned to receive Azvudine and symptomatic treatment (FNC group), or standard antiviral and symptomatic treatment (control group). The mean times of the first nucleic acid negative conversion (NANC) of ten patients in the FNC group and ten patients in the control group are 2.60 (SD 0.97; range 1-4) d and 5.60 (SD 3.06; range 2-13) d, respectively (p = 0.008). The mean times of the first NANC of four newly diagnosed subjects in the FNC group and ten subjects in the control group are 2.50 (SD 1.00; range 2-4) d and 9.80 (SD 4.73; range 3-19) d, respectively (starting from the initial treatment) (p = 0.01). No adverse events occur in the FNC group, while three adverse events occur in the control group (p = 0.06). The preliminary results show that FNC treatment in the mild and common COVID-19 may shorten the NANC time versus standard antiviral treatment. Therefore, clinical trials of FNC treating COVID-19 with larger sample size are warranted.
Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro
PLoS One2014 Aug 21;9(8):e105617.PMID: 25144636DOI: 10.1371/journal.pone.0105617
Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of Azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drugs and its drug resistance features. Azvudine exerted highly potent inhibition on HIV-1 (EC(50)s ranging from 0.03 to 6.92 nM) and HIV-2 (EC(50)s ranging from 0.018 to 0.025 nM). It also showed synergism in combination with six approved anti-HIV drugs on both C8166 and PBMC. In combination assay, the concentrations of Azvudine used were 1000 or 500 fold lower than other drugs. Azvudine also showed potent inhibition on NRTI-resistant strains (L74V and T69N). Although M184V caused 250 fold reduction in susceptibility, Azvudine remained active at nanomolar range. In in vitro induced resistant assay, the frequency of M184I mutation increased with induction time which suggests M184I as the key mutation in Azvudine treatment. As control, lamivudine treatment resulted in a higher frequency of M184I/V given the same induction time and higher occurrence of M184V was found. Molecular modeling analysis suggests that steric hindrance is more pronounced in mutant M184I than M184V due to the azido group of Azvudine. The present data demonstrates the potential of Azvudine as a complementary drug to current anti-HIV drugs. M184I should be the key mutation, however, Azvudine still remains active on HIV-1LAI-M184V at nanomolar range.