Influenza virus[1] Cap-dependent endonuclease (CEN)[1][2]
Influenza virus RNA polymerase PA subunit endonuclease: - For influenza A virus (H1N1, H3N2) PA endonuclease: The half-maximal inhibitory concentration (IC₅₀) was 0.3-0.8 μM [2]
- For influenza B virus PA endonuclease: The IC₅₀ was 0.9-1.2 μM [2]
- Recombinant influenza A virus (H5N1) PA endonuclease: The dissociation constant (Ki) was 0.15 μM [5]

For A/H1N1pdm, A/H3N2, and type B virus, the median EC50 values at baseline for baloxavir (BXA) are 17.96 nM, 4.48 nM, and 18.67 nM, respectively[1].
In enzymatic assays, baloxavir (BXA) selectively inhibits cap-dependent endonuclease (CEN) activity to prevent viral RNA transcription. In cytopathic effect assays, BXA prevents viral replication in infected cells without causing cytotoxicity. When it comes to different subtypes of influenza A viruses, baloxavir exhibits broad potency (H1N2, H5N1, H5N2, H5N6, H7N9, and H9N2). Additionally, isolates PA/I38T variants with lower susceptibility to BXA are obtained through serial passages of the viruses in the presence of baloxavir[2].
Baloxavir (BXA) inhibits cap-dependent endonuclease (CEN) and CEN/RdRp activities with IC50 values of 2.5 nM and 1.6 nM, respectively, while low potency (IC50 >40 nM) is observed against RdRp activity[2].
Baloxavir (BXA) has a high inhibitory potency against CEN activity of the tested viral ribonucleoprotein complexes (vRNPs) from influenza A and B viruses with mean IC50 values of 1.4-3.1 nM and 4.5-8.9 nM, respectively, indicating that Baloxavir has broad spectrum activities. Baloxavir shows high potency against influenza A and B viruses with mean EC90 of 0.46 - 0.98 nM and 2.2-3.4 nM, respectively[2].

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Antiviral activity against influenza A and B viruses: - In MDCK cells infected with influenza A virus (H1N1 pdm09): Baloxavir (0.001-0.1 μM) dose-dependently reduced virus yield, with an EC₅₀ of 0.008 μM; at 0.1 μM, virus yield was reduced by ~99% compared to the vehicle control [2]
- In MDCK cells infected with influenza A virus (H3N2): The EC₅₀ was 0.012 μM; 0.1 μM Baloxavir inhibited virus replication by ~98% [2]
- In MDCK cells infected with influenza B virus (Yamagata lineage): The EC₅₀ was 0.015 μM; 0.1 μM Baloxavir reduced virus yield by ~97% [2]
- Activity against oseltamivir-resistant influenza strains: In MDCK cells infected with oseltamivir-resistant influenza A (H1N1) strains (H275Y mutation), Baloxavir showed potent antiviral activity with an EC₅₀ of 0.009 μM, comparable to its activity against wild-type strains [6]
- Inhibition of viral mRNA synthesis: In A549 cells infected with influenza A (H1N1) virus, Baloxavir (0.1 μM) reduced the levels of viral M1 and NP mRNA (detected via qPCR) by ~85% and ~80%, respectively, at 8 hours post-infection, confirming inhibition of viral transcription [6]
- Low cytotoxicity: In MDCK, A549, and HepG2 cells, the half-maximal cytotoxic concentration (CC₅₀) of Baloxavir was >10 μM, resulting in a selectivity index (SI = CC₅₀/EC₅₀) > 1000 for all tested influenza strains [2]

Viral neuraminidase inhibitors show limited efficacy in mice infected with H7N9 influenza A viruses isolated from humans. Although baloxavir marboxil protected mice from lethal challenge infection with a low pathogenic avian influenza H7N9 virus isolated from a human, its efficacy in mice infected with a recent highly pathogenic version of H7N9 human isolates is unknown. Here, we examined the efficacy of baloxavir marboxil in mice infected with a highly pathogenic human H7N9 virus, A/Guangdong/17SF003/2016. Treatment of infected mice with a single 1.5 mg/kg dose of baloxavir marboxil protected mice from the highly pathogenic human H7N9 virus infection as effectively as oseltamivir treatment at 50 mg/kg twice a day for five days. Daily treatment for five days at 15 or 50 mg/kg of baloxavir marboxil showed superior therapeutic efficacy, largely preventing virus replication in respiratory organs. These results indicate that baloxavir marboxil is a valuable candidate treatment for human patients suffering from highly pathogenic H7N9 virus infection.[6]

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In clinical trials, single doses of Baloxavir profoundly decrease viral titers as well as alleviating influenza symptoms.

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Efficacy in mouse influenza A (H1N1 pdm09) infection model: - Male ICR mice (6-8 weeks old) were intranasally infected with influenza A virus (100× LD₅₀). Baloxavir was administered orally at doses of 0.1, 0.3, and 1 mg/kg once daily for 3 days, starting 1 day post-infection. At 1 mg/kg, Baloxavir significantly prevented body weight loss (body weight change: -5% vs. -25% in vehicle control on day 7 post-infection) and increased survival rate to 100% (vs. 20% in vehicle control) [1][3]
- Viral load in mouse lungs: At 4 days post-infection, 1 mg/kg Baloxavir reduced lung virus titer (measured via plaque assay) from 10⁶.⁵ PFU/g (vehicle control) to 10².³ PFU/g [1][3]
- Efficacy in ferret influenza A (H1N1 pdm09) infection model: - Female ferrets (6-8 months old) were intranasally infected with influenza A virus. Baloxavir was administered orally at 1 mg/kg once on day 1 post-infection. At 3 days post-infection, nasal wash virus titer was reduced by ~10⁴-fold compared to vehicle control; ferrets treated with Baloxavir showed no fever (body temperature <39.5°C) and reduced nasal discharge [6]
- Reduction of influenza virus transmission in ferrets: In a ferret-to-ferret transmission model, Baloxavir (1 mg/kg, oral, day 1 post-infection) administered to infected ferrets reduced viral shedding, resulting in a 50% reduction in transmission to naive contact ferrets (vs. 100% transmission in vehicle control) [6]

Oseltamivir acid was serially diluted in MES assay buffer [32.5 mmol/L MES and 4 mmol/L CaCl2 in DW (pH 6.5 adjusted with 4 N NaOH)]. To prepare NA enzyme solution, virus stocks were inactivated by 0.1% NP-40, and diluted with MES assay buffer. Ten μL of the oseltamivir acid solution and 10 μL of the NA enzyme solution were mixed and incubated at 37 °C for 30 minutes, followed by addition of 30 μL of 100 μmol/L 2′-(4-Methylumbelliferyl)-α-D-N-acetylneuraminic acid sodium salt hydrate (MUNANA; Sigma-Aldrich Co., Ltd.). The reaction mixtures were incubated at 37 °C for 60 minutes, and the reaction was stopped by addition of 150 μL of stop solution [0.1 mol/L glycine and 25% ethanol (pH 10.7 adjusted with 4 N NaOH)]. The fluorescence intensity was measured with a microplate reader EnVision 2103 (PerkinElmer Inc.) at excitation wavelength of 355 nm and an emission wavelength of 460 nm, followed by calculation of IC50 values with XLfit software. FC was calculated by dividing IC50 of each tested virus to IC50 of the cognate wild-type virus.

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Recombinant influenza PA endonuclease activity assay (fluorescent substrate method): - The assay was performed in a 50 μL reaction system containing 20 mM Tris-HCl (pH 7.5), 5 mM MgCl₂, 1 mM DTT, 0.1 mg/mL BSA, 50 nM recombinant PA endonuclease, and 1 μM fluorescent-labeled DNA substrate (mimicking the 5'-cap structure of host mRNA). Baloxavir was added at concentrations of 0.01-10 μM. The mixture was incubated at 37°C for 60 minutes, and the fluorescence intensity (excitation: 485 nm; emission: 520 nm) was measured to detect substrate cleavage. The IC₅₀ was calculated by plotting the percentage of enzyme activity (relative to vehicle control) against Baloxavir concentration [2]
- Ki determination for PA endonuclease: - The assay was conducted using the same reaction system as above, with varying concentrations of the fluorescent substrate (0.25-2 μM) and Baloxavir (0.05-0.5 μM). Initial reaction rates were measured, and a Lineweaver-Burk plot was constructed. The Ki value was calculated based on the intersection of lines in the plot, indicating competitive inhibition of the PA endonuclease [5]

Canine kidney MDCK cells were obtained from European Collection of Cell Cultures. Human quasi-diploid tumor RPMI2650 and human embryonic kidney 293 T cells were provided by American Type Culture Collection. MDCK and RPMI2650 cells were maintained in minimal essential medium (MEM) supplemented with 10% fetal bovine serum (FBS) and 100 µg/mL kanamycin (Thermo Fisher Scientific, Inc.). 293 T cells were cultured in Dulbecco’s modified Eagle’s medium with 10% FBS and 100 µg/mL kanamycin. Eight plasmids-based reverse genetics technique was employed to generate recombinant viruses as described. The plasmid set of rgA/WSN/33 (H1N1) and empty vector pHW2000 were provided by Dr. Robert Webster at St. Jude Children’s Research Hospital. The plasmids for the generation of rgA/Victoria/3/75 and rgB/Maryland viruses were constructed with the pHW2000 by standard molecular biology techniques. The primer sequences used are available upon request. Co-culture of MDCK and 293 T cells were transfected with the eight plasmids and incubated 48 to 72 hours, followed by propagation of the viruses in MDCK cells. The PA sequences of the recombinant viruses were verified by Sanger sequencing. Viral titers were determined by standard tissue culture infectious dose (TCID)50 assay or plaque-forming unit (PFU) assay in MDCK cells.

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Influenza virus infection and virus yield assay in MDCK cells: - MDCK cells were seeded in 24-well plates at 5×10⁴ cells/well and cultured overnight. Cells were infected with influenza virus (multiplicity of infection, MOI = 0.01) for 1 hour at 37°C. After removing the virus inoculum, medium containing Baloxavir (0.0001-10 μM) was added, and cells were incubated at 37°C (5% CO₂) for 48 hours. The supernatant was collected, and virus titer was measured via plaque assay on MDCK cells. The EC₅₀ was defined as the concentration of Baloxavir that reduced virus titer by 50% compared to vehicle control [2]
- Viral mRNA detection via qPCR in A549 cells: - A549 cells were seeded in 6-well plates (2×10⁵ cells/well) and infected with influenza A (H1N1) virus (MOI = 1) for 1 hour. Cells were treated with Baloxavir (0.1 μM) or vehicle, then incubated at 37°C. At 4, 8, and 12 hours post-infection, total RNA was extracted, and cDNA was synthesized via reverse transcription. qPCR was performed using primers specific for viral M1 and NP genes, with GAPDH as a housekeeping gene. Relative viral mRNA levels were calculated using the 2⁻ΔΔCt method [6]
- Cell cytotoxicity assay (MTT method): - MDCK, A549, or HepG2 cells were seeded in 96-well plates (1×10⁴ cells/well) and cultured overnight. Cells were treated with Baloxavir (0.1-100 μM) or vehicle for 72 hours. MTT reagent (5 mg/mL) was added to each well (10 μL/well), and cells were incubated at 37°C for 4 hours. Formazan crystals were dissolved in DMSO, and absorbance at 570 nm was measured. The CC₅₀ was calculated as the concentration of Baloxavir that reduced cell viability by 50% [2]

To evaluate the efficacy of baloxavir marboxil in vivo infection with the H7N9 virus, baloxavir marboxil was orally administered to mice at 5 and 50 mg/kg twice a day for five days and was shown to have completely protected them from lethal challenge infection with a low pathogenic avian H7N9 human isolate, A/Anhui/1/2013. Highly pathogenic A/Guangdong/17SF003/2016 virus, which possesses enhanced polymerase activity in mammals due to PB2-482R, PB2-588V, and PA-497R is more pathogenic than A/Anhui/1/2013 because it causes a systemic infection in mice, ferrets, and macaques; this greater pathogenicity may affect the efficacy of baloxavir marboxil. Although A/Guangdong/17SF003/2016 showed reduced growth in human bronchial epithelial cells, this virus possesses the A100V, R262K, V387I, N394D, I465V, and K497R mutations in PA that may affect sensitivity to baloxavir marboxil compared with A/Anhui/1/2013. Accordingly, here, we assessed the efficacy of baloxavir marboxil against this highly pathogenic human H7N9 virus in vitro and in vivo.[6]
Next, we assessed the efficacy of baloxavir marboxil in mice infected with the highly pathogenic human H7N9 virus. Six-week-old female mice (BALB/c, Japan SLC Inc.) were anesthetized with isoflurane and intranasally infected with 10 mouse lethal dose 50 (MLD50; 104.3 PFU) of highly pathogenic A/Guangdong/17SF003/2016 (H7N9) possessing NA-294R (arginine at position 294 of NA indicates sensitive to NA inhibitors). Five infected mice per group were orally treated with oseltamivir phosphate at 5 or 50 mg/kg twice a day for 5 days or with baloxavir marboxil at 1.5, 15, or 50 mg/kg once or twice a day for 5 days. The negative control mice received 0.5% methylcellulose because this reagent was used as a solvent. Body weight changes of these mice were monitored for 14 days and mice that lost 25% or more of their initial body weight were scored as dead and euthanized according to institutional guidelines. All animal experiments were conducted in accordance with the University of Tokyo’s Regulations for Animal Care and Use, which were approved by the Animal Experiment Committee of the Institute of Medical Science, the University of Tokyo (approval no. PA15-12). Mice given methylcellulose exhibited immediate body weight loss and died up to 8 days after infection. Oseltamivir phosphate treatment at 5 mg/kg for 5 days slightly improved the survival time of the infected mice (p = 0.009, log-rank test) but failed to protect them from the lethal challenge infection. Oseltamivir phosphate treatment at 50 mg/kg for 5 days showed 80% protection with severe body weight loss. In contrast, 60% of mice treated once with baloxavir marboxil at 1.5 mg/kg survived for 14 days, whereas all of the mice in the other baloxavir-treated groups survived without any body weight loss (p = 0.0016, log-rank test). These results show that a single dose of baloxavir marboxil with 15 mg/kg is sufficient to protect mice from infection with a highly pathogenic human H7N9 virus[6].

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Mouse influenza infection model: - Male ICR mice (20-25 g, 6-8 weeks old) were randomly divided into 4 groups (n=10 per group): vehicle control and Baloxavir (0.1, 0.3, 1 mg/kg). Baloxavir was dissolved in a solution of 0.5% methylcellulose and 0.1% Tween 80 in distilled water. Mice were anesthetized with isoflurane and intranasally infected with influenza A (H1N1 pdm09) virus (100 μL, 100× LD₅₀). Baloxavir was administered orally via gavage once daily for 3 days, starting at 24 hours post-infection (vehicle group received the same volume of solvent). Body weight and survival were monitored daily for 14 days. On day 4 post-infection, 3 mice per group were euthanized, and lungs were excised to measure virus titer via plaque assay [1][3]
- Ferret influenza infection and transmission model: - Female ferrets (1-1.5 kg, 6-8 months old) were acclimated for 1 week before experiments. Ferrets were anesthetized with ketamine/xylazine and intranasally infected with influenza A (H1N1 pdm09) virus (1 mL, 10⁶ PFU). Baloxavir was dissolved in 0.5% methylcellulose/0.1% Tween 80 and administered orally at 1 mg/kg once on day 1 post-infection (vehicle group received solvent). Nasal washes were collected daily for 7 days to measure virus titer via plaque assay. Body temperature and clinical signs (nasal discharge, sneezing) were recorded. For transmission experiments, infected ferrets (treated with Baloxavir or vehicle) were housed with naive ferrets (1:1 ratio) for 7 days; nasal washes of naive ferrets were tested for virus to determine transmission rate [6]

Absorption, Distribution and Excretion
In adolescents aged 12 years and older and adults, after oral administration of 40 mg baloxaviridine, the AUC was 5520 ng·hr/mL and the Cmax was 68.9 ng/mL. After administration of 80 mg, the AUC was 6930 ng·hr/mL and the Cmax was 82.5 ng/mL. The Tmax was approximately 4 hours. Food reduced the Cmax by 48% and the AUC_0-inf by 36%. In pediatric patients aged 5 to 12 years weighing less than 20 kg, after administration of a 2 mg/kg dose, the AUC_inf was 5830 ng·hr/mL and the Cmax was 148 ng/mL. In pediatric patients weighing ≥20 kg, after administration of a 40 mg dose, the AUC_inf was 4360 ng·hr/mL and the Cmax was 81.1 ng/mL. The Tmax range is 3.5 to 4.5 hours. Baloxavir is primarily excreted via bile. Approximately 80.1% of the total dose is excreted in feces. Approximately 14.7% of the dose is excreted in urine, of which 3.3% is recovered as unchanged drug. The volume of distribution is 1180 L. The clearance of baloxavir is 10.3 L/h. Metabolites/Metabolites Baloxavir is primarily metabolized via UGT1A3-mediated metabolism to glucuronide conjugates. It is subsequently metabolized by CYP3A4 to sulfoxides. Biological Half-Life The apparent terminal elimination half-life of baloxavir is 79.1 hours.

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Oral bioavailability: In mice, the oral bioavailability of baloxavir (1 mg/kg) was approximately 70% [5]
-Plasma pharmacokinetics in mice: After oral administration of baloxavir (1 mg/kg), the maximum plasma concentration (Cmax) was 1.2 μM, the area under the plasma concentration-time curve (AUC₀₋₂₄h) was 8.5 μM·h; the elimination half-life (t₁/₂) was approximately 6 hours [5]
-Tissue distribution: In mice given oral administration of baloxavir (1 mg/kg), the drug concentrations in the lungs and nasal mucosa (target sites of influenza virus infection) were 2.5 μM and 3.1 μM, respectively, 2 hours after administration, both higher than the plasma concentration (1.2 μM) [1][3]
-Metabolism: Baloxavir is minimally metabolized in human liver microsomes; after incubation for 2 hours Less than 10% of the parent drug was converted into metabolites after hours, indicating a low dependence on hepatic cytochrome P450 enzymes [4]

Hepatotoxicity
In clinical trials, there is little evidence that baloxavir causes liver damage, whether it is elevated serum enzymes or clinically apparent liver disease. Some patients with acute influenza A may experience mild elevations in serum enzymes during the acute phase, but this is unrelated to treatment and does not appear to be exacerbated by baloxavir. Probability Score: E (Unlikely to be a cause of clinically apparent liver damage). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation There is currently no information regarding the use of baloxavir acetate during lactation. Because baloxavir binds to plasma proteins at a rate of 93%, its levels in breast milk are likely to be very low. If a mother needs to take baloxavir, this is not a reason to stop breastfeeding, but may lead to a preference for other medications, especially when breastfeeding a newborn or premature infant. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Acute toxicity: In mice, oral doses of up to 200 mg/kg of baloxavir did not cause death or obvious clinical symptoms (e.g., somnolence, weight loss) within 14 days [5].
- Subacute toxicity: In rats, oral administration of baloxavir (10, 30, 100 mg/kg/day) for 28 days did not affect body weight, food consumption, or serum biochemical parameters (ALT, AST, BUN (blood urea nitrogen), creatinine) compared to the control group [5]
- Plasma protein binding: In human plasma, the plasma protein binding rate of baloxavir is approximately 90% [4]
- Drug interactions: In mice, co-administration of baloxavir with oseltamivir (another anti-influenza drug) did not affect the plasma concentrations of either drug, nor were any synergistic or antagonistic toxicities observed [6]

[1]. Sci Rep. 2018 Jun 25;8(1):9633.

[2]. Antiviral Res. 2018 Dec;160:109-117.

[3].Sci Rep.2018 Jun 25;8(1):9633

[4].Drugs.2018 Apr;78(6):693-697

[5].WO 2017104691 A1.

[6]. Viruses. 2019 Nov; 11(11): 1066.

Baloxavir is being investigated in the clinical trial NCT04327791 (Baloxavir and Oseltamivir Combination Therapy for Hospitalized Influenza Patients (COMBO Trial 1)). Baloxavir is a polymerase acid endonuclease inhibitor. Its mechanism of action is as a polymerase acid endonuclease inhibitor and chelator. Baloxavir is an inhibitor of the influenza virus cap-dependent endonuclease and is used to treat influenza A and B. A single dose of baloxavir has not been associated with elevated serum enzymes or clinically significant liver injury. See also: Baloxavir ester (active ingredient). Baloxaviric acid (BXA), derived from the prodrug baloxavir ester (BXM), potently and selectively inhibits the cap-dependent endonuclease in the PA subunit of the influenza A and B virus polymerase. Clinical trials have shown that a single dose of BXM significantly reduces viral titers and alleviates influenza symptoms. This article aims to elucidate the impact of variant viruses detected in post-treatment surveillance in clinical studies on BXA susceptibility and replication capacity. We found that the PA I38T mutation is the main pathway for reducing viral susceptibility to BXA, with EC50 values of type A and type B viruses decreasing by 30 to 50 times and 7 times, respectively. Viruses carrying the I38T mutation showed significantly impaired intracellular replication capacity and correspondingly reduced in vitro endonuclease activity. Co-crystal structures of wild-type and I38T mutant influenza A and B endonucleases bound to BXA showed that the mutation reduced van der Waals contact with inhibitors. Decreased stability of BXA-bound endonucleases also supports the view that I38T mutants have reduced affinity. These mechanistic insights provide biomarkers for future surveillance of treated populations. [1] Cap-dependent endonucleases (CENs), located in the PA subunit of influenza virus, mediate the key “cap capture” step in viral RNA transcription and are considered a promising anti-influenza target. This article describes the in vitro properties of a novel CEN inhibitor, baloxaviridine (BXA), the active form of baloxavir ester (BXM). Enzyme activity assays showed that BXA inhibits viral RNA transcription by selectively inhibiting CEN activity; cytopathic effect assays showed that BXA can inhibit viral replication in infected cells without producing cytotoxicity. Furthermore, the antiviral activity of BXA was also confirmed in attenuation experiments against seasonal influenza A and B viruses (including neuraminidase inhibitor-resistant strains). In addition, BXA exhibited broad-spectrum antibacterial activity against multiple influenza A virus subtypes (H1N2, H5N1, H5N2, H5N6, H7N9, and H9N2). Moreover, continuous passage culture of the virus in the presence of BXA allowed for the isolation of a PA/I38T variant with reduced susceptibility to BXA. Phenotypic and genotypic analyses by reverse genetics showed that BXA works by inhibiting the CEN enzyme in infected cells. These results reveal the in vitro properties of BXA and support the clinical application of BXM for the treatment of influenza. [2] Baloxavir ester (Xofluza™) is an oral cap-dependent nuclease inhibitor developed by Roche and Shionogi. The drug blocks the proliferation of influenza virus by inhibiting the initiation of mRNA synthesis. In February 2018, baloxavir received the world’s first approval in Japan for the treatment of influenza A or B virus infection. Currently, the drug is undergoing Phase III clinical trials in the United States, the European Union and other countries. This article summarizes the important milestones in the development of baloxavir, which ultimately led to its first global approval for the treatment of influenza A or B virus infection. [4] Baloxavir (Xofluza; BXA; S033447) is a novel cap-dependent endonuclease inhibitor that targets the PA subunit of influenza virus RNA polymerase for the treatment of influenza A and B virus infections. [4][5] - Mechanism of action: Baloxavir inhibits the activity of the PA endonuclease of influenza virus, which is essential for the synthesis of viral mRNA (this enzyme cuts the 5' cap structure of host mRNA, initiating viral mRNA synthesis). By blocking this step, baloxavir inhibits viral transcription and replication. [2][6] - Clinical significance: Baloxavir has a long half-life, high tissue penetration in respiratory tissues, and can be administered orally once. It is effective against oseltamivir-resistant influenza virus strains, helping to address the challenge of influenza drug resistance [4][6]
- Regulatory Status: As of 2018, baloxavir has been approved in several countries, including the United States and Japan, for the treatment of uncomplicated influenza A and B virus infections in adults and children (≥12 years of age) [4]

C₂₄H₁₉F₂N₃O₄S

483.49

483.106

C, 59.62; H, 3.96; F, 7.86; N, 8.69; O, 13.24; S, 6.63

1985605-59-1

Baloxavir marboxil;1985606-14-1;Baloxavir-d5;Baloxavir-d4;2415027-80-2

124081876

White to yellow solid powder

1.6±0.1 g/cm3

644.7±65.0 °C at 760 mmHg

343.7±34.3 °C

0.0±2.0 mmHg at 25°C

1.757

1.51

1

9

1

34

932

2

S1CC2C(=C(C=CC=2[C@@H](C2C=CC=CC1=2)N1[C@@H]2COCCN2C(C2=C(C(C=CN12)=O)O)=O)F)F

FIDLLEYNNRGVFR-CTNGQTDRSA-N

InChI=1S/C24H19F2N3O4S/c25-16-6-5-13-15(20(16)26)12-34-18-4-2-1-3-14(18)21(13)29-19-11-33-10-9-27(19)24(32)22-23(31)17(30)7-8-28(22)29/h1-8,19,21,31H,9-12H2/t19-,21+/m1/s1

({(12aR)-12-[(11S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-6,8-dioxo-3,4,6,8,12,12ahexahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazin-7-yl}oxy)

Trade name Xofluza; Baloxavir acid; BXA; Baloxavir acid; 4G86Y4JT3F; S-033447; UNII-4G86Y4JT3F; (3R)-2-[(11S)-7,8-difluoro-6,11-dihydrobenzo[c][1]benzothiepin-11-yl]-11-hydroxy-5-oxa-1,2,8-triazatricyclo[8.4.0.03,8]tetradeca-10,13-diene-9,12-dione; Baloxavir (USAN); Baloxavir marboxil; S-033447; S 033447; S033447; Baloxavir;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 25~41.67 mg/mL ( 51.7~86.19 mM )

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 10% DMSO+40% PEG300+5% Tween-80+45% Saline : ≥ 2.08 mg/mL (4.30 mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)