VV116
(Synonyms: JT001; GS-621763-d1 hydrobromide) 目录号 : GC64800
An antiviral agent and a derivative of remdesivir
Cas No.:2779498-79-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
VV116 is an antiviral agent and a derivative of the antiviral prodrug remdesivir .1 It inhibits viral replication of respiratory syncytial virus (RSV) in A549 cells (EC50 = 1.01 ?M). VV116 (25 mg/kg) decreases viral replication and lung viral titer counts in a mouse model of RSV infection. It also decreases alveolar inflammation in RSV-infected mice.
1.Zhang, R., Zhang, Y., Zheng, W., et al.Oral remdesivir derivative VV116 is a potent inhibitor of respiratory syncytial virus with efficacy in mouse modelSignal Transduct. Target. Ther.7(1)123(2022)
| Cas No. | 2779498-79-0 | SDF | |
| 别名 | JT001; GS-621763-d1 hydrobromide | ||
| 分子式 | C24H31DBrN5O7 | 分子量 | 583.45 |
| 溶解度 | DMSO : 250 mg/mL (428.49 mM; Need ultrasonic) | 储存条件 | 4°C, away from moisture |
| 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 | 1.7139 mL | 8.5697 mL | 17.1394 mL |
| 5 mM | 0.3428 mL | 1.7139 mL | 3.4279 mL |
| 10 mM | 0.1714 mL | 0.857 mL | 1.7139 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。
VV116 versus Nirmatrelvir-Ritonavir for Oral Treatment of Covid-19
N Engl J Med 2023 Feb 2;388(5):406-417.PMID:36577095DOI:10.1056/NEJMoa2208822.
Background: Nirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We conducted a phase 3, noninferiority, observer-blinded, randomized trial during the outbreak caused by the B.1.1.529 (omicron) variant of SARS-CoV-2. Symptomatic adults with mild-to-moderate Covid-19 with a high risk of progression were assigned to receive a 5-day course of either VV116 or nirmatrelvir-ritonavir. The primary end point was the time to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19-related target symptoms to a total score of 0 or 1 for the sum of each symptom (on a scale from 0 to 3, with higher scores indicating greater severity; total scores on the 11-item scale range from 0 to 33) for 2 consecutive days. A lower boundary of the two-sided 95% confidence interval for the hazard ratio of more than 0.8 was considered to indicate noninferiority (with a hazard ratio of >1 indicating a shorter time to sustained clinical recovery with VV116 than with nirmatrelvir-ritonavir). Results: A total of 822 participants underwent randomization, and 771 received VV116 (384 participants) or nirmatrelvir-ritonavir (387 participants). The noninferiority of VV116 to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery was established in the primary analysis (hazard ratio, 1.17; 95% confidence interval [CI], 1.01 to 1.35) and was maintained in the final analysis (median, 4 days with VV116 and 5 days with nirmatrelvir-ritonavir; hazard ratio, 1.17; 95% CI, 1.02 to 1.36). In the final analysis, the time to sustained symptom resolution (score of 0 for each of the 11 Covid-19-related target symptoms for 2 consecutive days) and to a first negative SARS-CoV-2 test did not differ substantially between the two groups. No participants in either group had died or had had progression to severe Covid-19 by day 28. The incidence of adverse events was lower in the VV116 group than in the nirmatrelvir-ritonavir group (67.4% vs. 77.3%). Conclusions: Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery, with fewer safety concerns. (Funded by Vigonvita Life Sciences and others; ClinicalTrials.gov number, NCT05341609; Chinese Clinical Trial Registry number, ChiCTR2200057856.).
An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants
Emerg Microbes Infect 2022 Dec;11(1):1518-1523.PMID:35579892DOI:10.1080/22221751.2022.2078230.
Omicron variant of SARS-CoV-2 has become the predominant variant worldwide. VV116 is an oral drug with robust anti-SARS-CoV-2 efficacy in preclinical studies. We conducted an open, prospective cohort study to evaluate its safety and effectiveness in Chinese participants infected with the omicron variant from March 8th, 2022 to March 24th, 2022. 136 hospitalized nonsevere patients confirmed with COVID-19 were enrolled including 60 patients who received VV116 (300 mg, BID×5 days) in the treatment group and 76 patients who didn't receive VV116 in the control group besides standard treatment. Viral load shedding time and adverse events were collected during the follow-up. There was no significant difference in baseline characteristics between the VV116 group and the control group, except for a higher symptom prevalence in the control group (P = 0.021). The median time from the first positive test to the first VV116 administration was 5 (range: 2-10) days. Participants who received VV116 within 5 days since the first positive test had a shorter viral shedding time than the control group (8.56 vs 11.13 days), and cox regression analysis showed adjusted HR of 2.37 [95%CI 1.50-3.75], P < 0.001. In symptomatic subgroup, VV116 group had a shorter viral shedding time than the control group (P = 0.016). A total of 9 adverse events with no serious adverse events were reported in the VV116 group, all of them were resolved without intervention. VV116 is a safe, effective oral antiviral drug, which shows a better performance within the early onset of omicron infection.
Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects
Acta Pharmacol Sin 2022 Dec;43(12):3130-3138.PMID:35296780DOI:10.1038/s41401-022-00895-6.
VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.
Structure genomics of SARS-CoV-2 and its Omicron variant: drug design templates for COVID-19
Acta Pharmacol Sin 2022 Dec;43(12):3021-3033.PMID:35058587DOI:10.1038/s41401-021-00851-w.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and persistently threatens to humanity. With tireless efforts from scientists around the world, understanding of the biology of coronavirus has been greatly enhanced over the past 2 years. Structural biology has demonstrated its powerful impact on uncovering structures and functions for the vast majority of SARS-CoV-2 proteins and guided the development of drugs and vaccines against COVID-19. In this review, we summarize current progress in the structural biology of SARS-CoV-2 and discuss important biological issues that remain to be addressed. We present the examples of structure-based design of Pfizer's novel anti-SARS-CoV-2 drug PF-07321332 (Paxlovid), Merck's nucleotide inhibitor molnupiravir (Lagevrio), and VV116, an oral drug candidate for COVID-19. These examples highlight the importance of structure in drug discovery to combat COVID-19. We also discussed the recent variants of Omicron and its implication in immunity escape from existing vaccines and antibody therapies.
VV116 as a potential treatment for COVID-19
Expert Opin Pharmacother 2023 Mar 20;1-4.PMID:36932818DOI:10.1080/14656566.2023.2193668.
Introduction: VV116 is a chemically-modified version of the antiviral remdesivir with oral bioavailability and potent activity against SARS-CoV-2. Areas covered: The optimal treatment of standard-risk outpatients who develop mild-to-moderate COVID-19 is controversial. While several therapeutic are currently recommended, including nirmatrelvir-ritonavir (Paxlovid), molnupiravir, and remdesivir, these treatments have substantial drawbacks, including drug-drug interactions and questionable efficacy in vaccinated adults. Novel therapeutic options are urgently needed. Expert opinion: On 28 December 2022, a phase 3, observer-blinded, randomized trial was published evaluating 771 symptomatic adults with mild-to-moderate COVID-19 with a high risk of progression to severe disease. Participants were assigned to receive a 5-day course of either Paxlovid)\, which is recommended by the World Health Organization for treating mild-to-moderate COVID-19, or VV116 and the primary end point was the time to sustained clinical recovery through day 28. Among study subjects, VV116 was found to be noninferior to Paxlovid with respect to the time to sustained clinical recovery and with fewer safety concerns. This manuscript examines what is known about VV116 and explores how this novel treatment option may be used in the future to address the ongoing SARS-CoV-2 pandemic.