Remdesivir (GS-5734)
(Synonyms: 瑞德西韦; GS-5734) 目录号 : GC32223
A prodrug form of GS-443902
Cas No.:1809249-37-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Remdesivir is a prodrug form of the antiviral nucleotide analog GS-443902.1,2,3 Upon entry into cells, remdesivir is metabolized into the intermediate metabolite GS-441524 , which is then further metabolized to the active nucleotide triphosphate GS-443902 that induces RNA chain termination and inhibits viral polymerases.4 Remdesivir reduces viral titers in primary human airway epithelial (HAE) cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV) or severe acute respiratory syndrome CoV (SARS-CoV; EC50s = 0.074 and 0.069 ?M, respectively). It reduces infectious virus production in SARS-CoV-2-infected HAE cells (EC50 = 10 nM).5 In vivo, remdesivir (25 and 50 mg/kg) reduces lung viral titers and prevents weight loss in a mouse model of SARS-CoV infection.2 Remdesivir (25 mg/kg) also reduces lung viral titers and lung hemorrhage and improves pulmonary function in mice infected with a chimeric SARS-CoV encoding the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).5 Formulations containing remdesivir have been used in the treatment of COVID-19.
瑞德西韦是一种抗病毒核苷酸类似物GS-443902的前药形式。1,2,3 进入细胞后，瑞德西韦被代谢成中间代谢物GS-441524，进一步代谢为活性核苷酸三磷酸GS-443902，诱导RNA链终止并抑制病毒聚合酶。4 瑞德西韦可以减少中东呼吸综合症冠状病毒（MERS-CoV）或严重急性呼吸综合症冠状病毒（SARS-CoV）感染的人类气道上皮原代细胞（HAE）中的病毒滴度（EC50分别为0.074和0.069μM）。它可以降低SARS-CoV-2感染的HAE细胞中的传染性病毒产量（EC50 = 10 nM）。5在体内，瑞德西韦（25和50 mg/kg）可以减少SARS-CoV感染小鼠的肺病毒滴度，并防止体重下降。2 瑞德西韦（25 mg/kg）还可以减少感染编码SARS-CoV-2 RNA依赖性RNA聚合酶（RdRp）的嵌合SARS-CoV感染小鼠的肺病毒滴度和肺出血，并改善肺功能。5 含瑞德西韦的制剂已用于COVID-19的治疗
1.Agostini, M.L., Andres, E.L., Sims, A.C., et al.Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonucleasemBio9(2)e00221-00218(2018) 2.Sheahan, T.P., Sims, A.C., Graham, R.L., et al.Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronavirusesSci. Transl. Med.9(396)eaal3653(2017) 3.Cox, R.M., Wolf, J.D., Lieber, C.M., et al.Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferretsNat. Commun.12(1)6415(2021) 4.Eastman, R.T., Roth, J.S., Brimacombe, K.R., et al.Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19ACS Cent. Sci.6(5)672-683(2020) 5.Pruijssers, A.J., George, A.S., Sch?fer, A., et al.Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in miceCell Rep.32(3)107940(2020)
| Cas No. | 1809249-37-3 | SDF | |
| 别名 | 瑞德西韦; GS-5734 | ||
| 化学名 | (2S)-2-ethylbutyl 2-(((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate | ||
| Canonical SMILES | N#C[C@@]1(C2=CC=C3N2N=CN=C3N)O[C@H](COP(OC4=CC=CC=C4)(N[C@@H](C)C(OCC(CC)CC)=O)=O)[C@@H](O)[C@H]1O | ||
| 分子式 | C27H35N6O8P | 分子量 | 602.58 |
| 溶解度 | DMSO : ≥ 125 mg/mL (207.44 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6595 mL | 8.2977 mL | 16.5953 mL |
| 5 mM | 0.3319 mL | 1.6595 mL | 3.3191 mL |
| 10 mM | 0.166 mL | 0.8298 mL | 1.6595 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。
Remdesivir (GS-5734) in COVID-19 Therapy: The Fourth Chance
Curr Drug Targets 2021;22(12):1346-1356.PMID:33267759DOI:10.2174/1389450121999201202110303.
Background: Since its initial start in December 2019 at Wuhan, China, the coronavirus disease 2019 (COVID-19) has been rapidly spreading and labelled as a pandemic by the World Health Organization. The rate of human to human transmission of COVID-19 is far higher than severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome coronavirus (MERS). With no drugs or vaccines approved for the treatment of the disease, physicians have been using pre-existing drugs to curb the disease. One potential anti-viral agent currently undergoing numerous clinical trials is remdesivir, a nucleotide analog that inhibits RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: In this mini-review, we provide an overview of remdesivir's journey, mechanism of action, pharmacokinetics, used in patients with COVID-19 under compassionate use principle and clinical trials to understand the effect of remdesivir in the treatment of patients with COVID-19. Conclusion: Initially, remdesivir was granted an emergency use authorization (EUA) by the U.S. Food and Drug Administration for the treatment of COVID-19 with severe disease. But now, remdesivir has been granted for use under EUA to treat all hospitalized COVID-19 patients, irrespective of their severity of disease.
Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial
Lancet 2020 May 16;395(10236):1569-1578.PMID:32423584DOI:10.1016/S0140-6736(20)31022-9.
Background: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged 鈮?8 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1路23 [95% CI 0路87-1路75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1路52 [0路95-2路43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.
Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition
Front Microbiol 2020 Jun 12;11:1105.PMID:32595613DOI:10.3389/fmicb.2020.01105.
Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal neurological complications. Currently, no registered antivirals have been approved for clinical therapy. Thus, a therapeutic agent for the enterovirus-related disease is urgently needed. Remdesivir (GS-5734) is a novel monophosphoramidate adenosine analog prodrug that exhibits potent antiviral activity against diverse RNA virus families, including positive-sense Coronaviridae and Flaviviridae and negative-sense Filoviridae, Paramyxoviridae, and Pneumoviridae. Currently, remdesivir is under phase 3 clinical development for disease COVID-19 treatment. Here, we found that remdesivir impeded both EV71 viral RNA (vRNA) and complementary (cRNA) synthesis, indicating that EV71 replication is inhibited by the triphosphate (TP) form of remdesivir. Moreover, remdesivir showed potent antiviral activity against diverse enteroviruses. These data extend the remdesivir antiviral activity to enteroviruses and indicate that remdesivir is a promising antiviral treatment for EV71 and other enterovirus infections.
Remdesivir (GS-5734) Is Efficacious in Cynomolgus Macaques Infected With Marburg Virus
J Infect Dis 2020 Nov 9;222(11):1894-1901.PMID:32479636DOI:10.1093/infdis/jiaa290.
Marburg virus (MARV) is a filovirus with documented human case-fatality rates of up to 90%. Here, we evaluated the therapeutic efficacy of Remdesivir (GS-5734) in nonhuman primates experimentally infected with MARV. Beginning 4 or 5 days post inoculation, cynomolgus macaques were treated once daily for 12 days with vehicle, 5 mg/kg remdesivir, or a 10-mg/kg loading dose followed by 5 mg/kg remdesivir. All vehicle-control animals died, whereas 83% of animals receiving a 10-mg/kg loading dose of remdesivir survived, as did 50% of animals receiving a 5-mg/kg remdesivir regimen. Remdesivir-treated animals exhibited improved clinical scores, lower plasma viral RNA, and improved markers of kidney function, liver function, and coagulopathy versus vehicle-control animals. The small molecule remdesivir showed therapeutic efficacy in this Marburg virus disease model with treatment initiation 5 days post inoculation, supporting further assessment of remdesivir for the treatment of Marburg virus disease in humans.
Remdesivir: First Approval
Drugs 2020 Sep;80(13):1355-1363.PMID:32870481DOI:10.1007/s40265-020-01378-w.
The antiviral agent Remdesivir (Veklury庐; Gilead Sciences), nucleotide analogue prodrug, has broad-spectrum activity against viruses from several families. Having demonstrated potent antiviral activity against coronaviruses in preclinical studies, Remdesivir emerged as a candidate drug for the treatment of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, during the current global pandemic. Phase III evaluation of Remdesivir in the treatment of COVID-19 commenced in early 2020 and has thus far yielded promising results. In late May 2020, Taiwan conditionally approved the use of Remdesivir in patients with severe COVID-19. This was followed by a rapid succession of conditional approvals in various countries/regions including the EU and Canada. Preceding these conditional approvals, an emergency use authorization for Remdesivir had been granted in the USA (on 1 May 2020) and a special approval for emergency use was granted in Japan (on 7 May 2020). This article summarizes the milestones in the development of Remdesivir leading to its first conditional approval for the treatment of COVID-19.