Baloxavir marboxil
(Synonyms: 巴洛沙韦酯,S-033188) 目录号 : GC35465
A prodrug form of the antiviral baloxavir acid
Cas No.:1985606-14-1
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
Baloxavir marboxil is a prodrug form of the antiviral and influenza virus cap-dependent endonuclease (CEN) inhibitor baloxavir acid.1,2 It inhibits influenza CEN and CEN/RNA-dependent RNA polymerase (CEN/RdRp) activity in cell-free assays (IC50s = 530 and 340 nM, respectively).2 Baloxavir marboxil prevents mortality in a mouse model of influenza A and B viral infection when administered at a dose of 5 or 50 mg/kg twice in a single day.1 It also reduces lung viral titers, body weight loss, and mortality in a mouse model of influenza A and B viral infection when administered 72 hours post-infection at 50 mg/kg. Formulations containing baloxavir marboxil have been used in the early treatment of uncomplicated influenza.
1.Fukao, K., Ando, Y., Noshi, T., et al.Baloxavir marboxil, a novel cap-dependent endonuclease inhibitor potently suppresses influenza virus replication and represents therapeutic effects in both immunocompetent and immunocompromised mouse modelsPLoS One14(5)e0217307(2019) 2.Noshi, T., Kitano, M., Taniguchi, K., et al.In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunitAntiviral Res.160109-117(2017)
| Cas No. | 1985606-14-1 | SDF | |
| 别名 | 巴洛沙韦酯,S-033188 | ||
| Canonical SMILES | O=C(C=C1)C(OCOC(OC)=O)=C2N1N([C@H]3C4=CC=C(F)C(F)=C4CSC5=CC=CC=C35)[C@@]6([H])N(CCOC6)C2=O | ||
| 分子式 | C27H23F2N3O7S | 分子量 | 571.55 |
| 溶解度 | DMSO: 33.33 mg/mL (58.32 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 | 1.7496 mL | 8.7481 mL | 17.4963 mL |
| 5 mM | 0.3499 mL | 1.7496 mL | 3.4993 mL |
| 10 mM | 0.175 mL | 0.8748 mL | 1.7496 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。
Baloxavir marboxil for Uncomplicated Influenza in Adults and Adolescents
N Engl J Med 2018 Sep 6;379(10):913-923.PMID:30184455DOI:10.1056/NEJMoa1716197.
Background: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents. Methods: We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population. Results: In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively. Conclusions: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).
Baloxavir marboxil
Hosp Pharm 2019 Jun;54(3):165-169.PMID:31205326DOI:10.1177/0018578719841044.
Each month, subscribers to The Formulary Monograph Service receive 5 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433.
Baloxavir marboxil: A Review in Acute Uncomplicated Influenza
Drugs 2020 Jul;80(11):1109-1118.PMID:32601915DOI:10.1007/s40265-020-01350-8.
Baloxavir marboxil (Xofluza®; hereafter referred to as baloxavir), the prodrug of baloxavir acid, is a first-in-class, small molecule inhibitor of the polymerase acidic (PA) protein subunit of the influenza virus polymerase complex. Baloxavir (after conversion to baloxavir acid) acts to block influenza virus replication by inhibiting the cap-dependent endonuclease activity of the PA protein. Taken orally as a single dose, baloxavir is approved in the USA for the treatment of acute uncomplicated influenza in patients ≥ 12 years of age who have been symptomatic for ≤ 48 h. Data from randomized, double-blind, placebo- and oseltamivir-controlled phase III trials have shown that baloxavir is efficacious in improving influenza symptoms both in otherwise healthy adolescents and adults and in those at high risk of influenza complications, displaying similar efficacy to that of oseltamivir. Furthermore, there is evidence that baloxavir can reduce influenza viral load more rapidly than oseltamivir. Baloxavir has activity against influenza A and B viruses (including strains resistant to neuraminidase inhibitors) and is well tolerated. Evidence of the emergence and likely human-to-human transmission of variant viruses with reduced susceptibility to baloxavir highlights the importance of monitoring and surveillance for changes in influenza virus drug susceptibility patterns. However, currently available evidence suggests that baloxavir, with the benefits of a single oral dose regimen, provides a useful alternative to neuraminidase inhibitors for the treatment of acute uncomplicated influenza in adolescents and adults.
Baloxavir marboxil: The First Cap-Dependent Endonuclease Inhibitor for the Treatment of Influenza
Ann Pharmacother 2019 Jul;53(7):754-759.PMID:30674196DOI:10.1177/1060028019826565.
Objective: To review the pharmacology, pharmacokinetics, clinical trials, and clinical implications of Baloxavir marboxil. Data sources: A MEDLINE search was conducted using the terms baloxavir, Baloxavir marboxil, cap-dependent endonuclease inhibitor, and polymerase acidic endonuclease inhibitor. Additional data were obtained from the prescribing information and relevant guidelines. Study selection and data extraction: All clinical trials were included. Data synthesis: Baloxavir marboxil exploits a new mechanism of action of inhibiting cap-dependent endonuclease. Baloxavir was shown to be superior compared with placebo and noninferior compared with oseltamivir with regard to the primary end point. Baloxavir was well tolerated in the trials. A second phase III study investigating high-risk patients was completed with positive results. However, the full article is not yet published. Relevance to Patient Care and Clinical Practice: The small amount of literature limits baloxavir's use in certain patient populations. Baloxavir offers advantages such as single-dose regimen, eliminating adherence concerns and lack of cross-resistance, making it an alternative for resistant viruses. Several uncertainties remain. Baloxavir has not been studied in hospitalized patients, patients with symptoms for >48 hours, or in combination with other antiviral agents. Furthermore, resistance to baloxavir can develop after 1 dose. Clinical studies are ongoing to evaluate baloxavir in young pediatric patients, hospitalized patients, and in combination therapy with neuraminidase inhibitors to further elucidate baloxavir's place in therapy. Conclusion: Baloxavir is a new antiviral medication for the treatment of influenza. Given the new mechanism of action, baloxavir may be useful in treating patients with resistant viruses.
Baloxavir marboxil: An Original New Drug against Influenza
Pharmaceuticals (Basel) 2021 Dec 24;15(1):28.PMID:35056085DOI:10.3390/ph15010028.
Baloxavir marboxil is a new drug developed in Japan by Shionogi to treat seasonal flu infection. This cap-dependent endonuclease inhibitor is a prodrug that releases the biologically active baloxavir acid. This new medicine has been marketed in Japan, the USA and Europe. It is well tolerated (more than 1% of the patients experienced diarrhea, bronchitis, nausea, nasopharyngitis, and headache), and both influenza A and B viruses are sensitive, although the B strain is more resistant due to variations in the amino acid residues in the binding site. The drug is now in post-marketing pharmacovigilance phase, and its interest will be especially re-evaluated in the future during the annual flu outbreaks. It has been also introduced in a recent clinical trial against COVID-19 with favipiravir.