Baloxavir marboxil
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MedKoo CAT#: 329490

CAS#: 1985606-14-1

Description: Baloxavir marboxil, also known as S 033188, 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.


Chemical Structure

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Baloxavir marboxil
CAS# 1985606-14-1

Theoretical Analysis

MedKoo Cat#: 329490
Name: Baloxavir marboxil
CAS#: 1985606-14-1
Chemical Formula: C27H23F2N3O7S
Exact Mass: 571.12
Molecular Weight: 571.552
Elemental Analysis: C, 56.74; H, 4.06; F, 6.65; N, 7.35; O, 19.59; S, 5.61

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3750 Ready to ship
2g USD 5850 Ready to ship
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Related CAS #: 1985605-59-1 (Baloxavir)   1985606-14-1    

Synonym: Baloxavir marboxil; S 033188; S-033188; S033188; Xofluza;

IUPAC/Chemical Name: ({(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)methyl methyl carbonate

InChi Key: RZVPBGBYGMDSBG-GGAORHGYSA-N

InChi Code: InChI=1S/C27H23F2N3O7S/c1-36-27(35)39-14-38-25-19(33)8-9-31-24(25)26(34)30-10-11-37-12-21(30)32(31)23-15-6-7-18(28)22(29)17(15)13-40-20-5-3-2-4-16(20)23/h2-9,21,23H,10-14H2,1H3/t21-,23+/m1/s1

SMILES Code: O=C(OCOC(C(C=C1)=O)=C(N1N([C@@H]2C3=CC=CC=C3SCC4=C(F)C(F)=CC=C24)[C@@]5([H])N6CCOC5)C6=O)OC

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Baloxavir marboxil (S-033188) is a selective inhibitor of influenza cap-dependent endonuclease and a potent antiviral agent that has activity against influenza A and B virus.
In vitro activity: To evaluate the inhibitory effects of BXA (baloxavir acid, the active form of baloxavir marboxil) against various types of viruses, clinical isolates and animal-derived influenza viruses were subjected to susceptibility testing. BXA exhibited high potency against clinical isolates from influenza A and B viruses with mean EC90 values ranging from 0.63 to 0.95 nM and 6.1–6.5 nM, respectively. When tested with various subtypes of animal influenza A viruses (H1N2, H5N1, H5N2, H5N6, H7N9, and H9N2), the inhibitory potency of BXA was comparable to the levels seen with H1N1 and H3N2 viruses (Table 3). The mean EC50 values of BXA for these strains of influenza A and B viruses, which included a NAI-resistant strain, ranged from 0.20 to 1.9 nM and 3.3–13 nM, respectively (Table S1). The results suggest that BXA has both potent and broad activity against influenza A and B viruses compared to the other marketed drugs, including strains from laboratory, clinical isolates, and recent vaccine strains. To confirm that BXA targets CEN activity in infected cells, viral mRNA, vRNA and cRNA levels in the presence of BXA were quantified with the A/WSN/33-infected cells. At 5 h post-infection, BXA inhibited viral mRNA, vRNA, and cRNA synthesis in infected cells with mean EC90 values of 13, 13, and 16 nM, respectively (Fig. 3). Intriguingly, BXA achieved 4 log10 reduction in mRNA levels at a lower concentration than favipiravir.The results suggest that BXA blocks viral mRNA, vRNA and cRNA synthesis at the early stage of viral replication in infected cells. Antiviral Res. 2018 Dec;160:109-117. https://pubmed.ncbi.nlm.nih.gov/30316915/
In vivo activity: In this study, the antiviral effects of BXM (baloxavir marboxil) against influenza A virus infection in the ferret model were examined. The maximum virus titer in nasal washes in vehicle‐treated ferrets was detected on Day 2 p.i., followed by a decline by Day 3 p.i. (Figure 3B). BXM at doses of 10 and 30 mg/kg showed a similar reduction in virus titer to an undetectable level (ie, <0.5 log10 TCID50/mL) at Day 2 p.i. The suppression of body temperature changes over time from 8 hours up to Day 3 p.i. was significantly greater with BXM at doses of 10 and 30 mg/kg than vehicle and OSP 5 mg/kg. In the second part of the experiments, ferrets were infected with influenza A/Kadoma/3/2006 (H1N1) strain intranasally at 5000 TCID50/ferret, which was a fivefold higher infectious dose increasing the body temperature by >1° by Day 2 p.i. BXM treatment at Day 2 for 1 day at the dose of 10 mg/kg resulted in a statistically significant reduction in virus titer by Day 3. These results highlight the magnitude and rapidity of the antiviral effects of BXM against influenza A virus infection. Influenza Other Respir Viruses. 2020 Nov; 14(6): 710–719. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578299/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 45.0 78.73

Preparing Stock Solutions

The following data is based on the product molecular weight 571.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Noshi T, Kitano M, Taniguchi K, Yamamoto A, Omoto S, Baba K, Hashimoto T, Ishida K, Kushima Y, Hattori K, Kawai M, Yoshida R, Kobayashi M, Yoshinaga T, Sato A, Okamatsu M, Sakoda Y, Kida H, Shishido T, Naito A. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Res. 2018 Dec;160:109-117. doi: 10.1016/j.antiviral.2018.10.008. Epub 2018 Oct 11. PMID: 30316915. 2. Taniguchi K, Ando Y, Nobori H, Toba S, Noshi T, Kobayashi M, Kawai M, Yoshida R, Sato A, Shishido T, Naito A, Matsuno K, Okamatsu M, Sakoda Y, Kida H. Inhibition of avian-origin influenza A(H7N9) virus by the novel cap-dependent endonuclease inhibitor baloxavir marboxil. Sci Rep. 2019 Mar 5;9(1):3466. doi: 10.1038/s41598-019-39683-4. PMID: 30837531; PMCID: PMC6401108. 3. Noshi T, Kitano M, Taniguchi K, Yamamoto A, Omoto S, Baba K, Hashimoto T, Ishida K, Kushima Y, Hattori K, Kawai M, Yoshida R, Kobayashi M, Yoshinaga T, Sato A, Okamatsu M, Sakoda Y, Kida H, Shishido T, Naito A. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Res. 2018 Dec;160:109-117. doi: 10.1016/j.antiviral.2018.10.008. Epub 2018 Oct 11. PMID: 30316915. 4. Taniguchi K, Ando Y, Nobori H, Toba S, Noshi T, Kobayashi M, Kawai M, Yoshida R, Sato A, Shishido T, Naito A, Matsuno K, Okamatsu M, Sakoda Y, Kida H. Inhibition of avian-origin influenza A(H7N9) virus by the novel cap-dependent endonuclease inhibitor baloxavir marboxil. Sci Rep. 2019 Mar 5;9(1):3466. doi: 10.1038/s41598-019-39683-4. PMID: 30837531; PMCID: PMC6401108.
In vitro protocol: 1. Noshi T, Kitano M, Taniguchi K, Yamamoto A, Omoto S, Baba K, Hashimoto T, Ishida K, Kushima Y, Hattori K, Kawai M, Yoshida R, Kobayashi M, Yoshinaga T, Sato A, Okamatsu M, Sakoda Y, Kida H, Shishido T, Naito A. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Res. 2018 Dec;160:109-117. doi: 10.1016/j.antiviral.2018.10.008. Epub 2018 Oct 11. PMID: 30316915. 2. Taniguchi K, Ando Y, Nobori H, Toba S, Noshi T, Kobayashi M, Kawai M, Yoshida R, Sato A, Shishido T, Naito A, Matsuno K, Okamatsu M, Sakoda Y, Kida H. Inhibition of avian-origin influenza A(H7N9) virus by the novel cap-dependent endonuclease inhibitor baloxavir marboxil. Sci Rep. 2019 Mar 5;9(1):3466. doi: 10.1038/s41598-019-39683-4. PMID: 30837531; PMCID: PMC6401108.
In vivo protocol: 1. Kiso M, Yamayoshi S, Murakami J, Kawaoka Y. Baloxavir Marboxil Treatment of Nude Mice Infected With Influenza A Virus. J Infect Dis. 2020 Apr 27;221(10):1699-1702. doi: 10.1093/infdis/jiz665. PMID: 31837268; PMCID: PMC7184910. 2. Kitano M, Matsuzaki T, Oka R, Baba K, Noda T, Yoshida Y, Sato K, Kiyota K, Mizutare T, Yoshida R, Sato A, Kamimori H, Shishido T, Naito A. The antiviral effects of baloxavir marboxil against influenza A virus infection in ferrets. Influenza Other Respir Viruses. 2020 Nov;14(6):710-719. doi: 10.1111/irv.12760. Epub 2020 Jun 13. PMID: 32533654; PMCID: PMC7578299.

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1: Influenza vaccine for 2019-2020. Med Lett Drugs Ther. 2019 Oct 21;61(1583):161-166. PubMed PMID: 31770355.

2: Imai M, Yamashita M, Sakai-Tagawa Y, Iwatsuki-Horimoto K, Kiso M, Murakami J, Yasuhara A, Takada K, Ito M, Nakajima N, Takahashi K, Lopes TJS, Dutta J, Khan Z, Kriti D, van Bakel H, Tokita A, Hagiwara H, Izumida N, Kuroki H, Nishino T, Wada N, Koga M, Adachi E, Jubishi D, Hasegawa H, Kawaoka Y. Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets. Nat Microbiol. 2019 Nov 25. doi: 10.1038/s41564-019-0609-0. [Epub ahead of print] PubMed PMID: 31768027.

3: Yoshino R, Yasuo N, Sekijima M. Molecular Dynamics Simulation reveals the mechanism by which the Influenza Cap-dependent Endonuclease acquires resistance against Baloxavir marboxil. Sci Rep. 2019 Nov 25;9(1):17464. doi: 10.1038/s41598-019-53945-1. PubMed PMID: 31767949.

4: Kiso M, Yamayoshi S, Furusawa Y, Imai M, Kawaoka Y. Treatment of Highly Pathogenic H7N9 Virus-Infected Mice with Baloxavir Marboxil. Viruses. 2019 Nov 15;11(11). pii: E1066. doi: 10.3390/v11111066. PubMed PMID: 31731678.

5: Seki M, Sakai-Tagawa Y, Yasuhara A, Watanabe Y. Adult influenza A (H3N2) with reduced susceptibility to baloxavir or peramivir cured after switching anti-influenza agents. IDCases. 2019 Oct 1;18:e00650. doi: 10.1016/j.idcr.2019.e00650. eCollection 2019. PubMed PMID: 31692637; PubMed Central PMCID: PMC6804930.

6: Ye C, Wang D, Liu H, Ma H, Dong Y, Yao M, Wang Y, Zhang H, Zhang L, Cheng L, Xu Z, Lei Y, Zhang F, Ye W. An Improved Enzyme-Linked Focus Formation Assay Revealed Baloxavir Acid as a Potential Antiviral Therapeutic Against Hantavirus Infection. Front Pharmacol. 2019 Oct 16;10:1203. doi: 10.3389/fphar.2019.01203. eCollection 2019. PubMed PMID: 31680975; PubMed Central PMCID: PMC6807675.

7: Hui DS, Ng SS. Recommended hospital preparations for future cases and outbreaks of novel influenza viruses. Expert Rev Respir Med. 2019 Oct 29:1-10. doi: 10.1080/17476348.2020.1683448. [Epub ahead of print] PubMed PMID: 31648548.

8: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK547923/ PubMed PMID: 31643258.

9: Leuba A, Lagnaux N, Cinoa A, Schnetz E, Genné D. [Antiviral therapy for general practitioners]. Rev Med Suisse. 2019 Oct 9;15(666):1825-1830. Review. French. PubMed PMID: 31599524.

10: Miskulin DC. Influenza in dialysis patients: an opportunity to decrease mortality? Curr Opin Nephrol Hypertens. 2019 Nov;28(6):607-614. doi: 10.1097/MNH.0000000000000550. PubMed PMID: 31567466.

11: Chesnokov A, Patel MC, Mishin VP, De La Cruz JA, Lollis L, Nguyen HT, Dugan V, Wentworth DE, Gubareva LV. Replicative fitness of seasonal influenza A viruses with decreased susceptibility to baloxavir. J Infect Dis. 2019 Sep 21. pii: jiz472. doi: 10.1093/infdis/jiz472. [Epub ahead of print] PubMed PMID: 31541547.

12: Hirotsu N, Sakaguchi H, Sato C, Ishibashi T, Baba K, Omoto S, Shishido T, Tsuchiya K, Hayden FG, Uehara T, Watanabe A. Baloxavir marboxil in Japanese pediatric patients with influenza: safety and clinical and virologic outcomes. Clin Infect Dis. 2019 Sep 20. pii: ciz908. doi: 10.1093/cid/ciz908. [Epub ahead of print] PubMed PMID: 31538644.

13: Nemoto M, Tamura N, Bannai H, Tsujimura K, Kokado H, Ohta M, Yamanaka T. Mutated influenza A virus exhibiting reduced susceptibility to baloxavir marboxil from an experimentally infected horse. J Gen Virol. 2019 Nov;100(11):1471-1477. doi: 10.1099/jgv.0.001325. PubMed PMID: 31526451.

14: Takashita E, Ichikawa M, Morita H, Ogawa R, Fujisaki S, Shirakura M, Miura H, Nakamura K, Kishida N, Kuwahara T, Sugawara H, Sato A, Akimoto M, Mitamura K, Abe T, Yamazaki M, Watanabe S, Hasegawa H, Odagiri T. Human-to-Human Transmission of Influenza A(H3N2) Virus with Reduced Susceptibility to Baloxavir, Japan, February 2019. Emerg Infect Dis. 2019 Nov;25(11):2108-2111. doi: 10.3201/eid2511.190757. Epub 2019 Nov 17. PubMed PMID: 31436527; PubMed Central PMCID: PMC6810216.

15: Checkmahomed L, M'hamdi Z, Carbonneau J, Venable MC, Baz M, Abed Y, Boivin G. Impact of the baloxavir-resistant polymerase acid (PA) I38T substitution on the fitness of contemporary influenza A(H1N1)pdm09 and A(H3N2) strains. J Infect Dis. 2019 Aug 16. pii: jiz418. doi: 10.1093/infdis/jiz418. [Epub ahead of print] PubMed PMID: 31419295.

16: Szollosi DE, Bill A. Potential Role of Endonuclease Inhibition and Other Targets in the Treatment of Influenza. Curr Drug Targets. 2019 Aug 1. doi: 10.2174/1389450120666190801115130. [Epub ahead of print] PubMed PMID: 31368872.

17: Gubareva LV, Fry AM. Baloxavir and Treatment-Emergent Resistance: Public Health Insights and Next Steps. J Infect Dis. 2019 Jul 16. pii: jiz245. doi: 10.1093/infdis/jiz245. [Epub ahead of print] PubMed PMID: 31309982.

18: Uehara T, Hayden FG, Kawaguchi K, Omoto S, Hurt AC, De Jong MD, Hirotsu N, Sugaya N, Lee N, Baba K, Shishido T, Tsuchiya K, Portsmouth S, Kida H. Treatment-Emergent Influenza Variant Viruses With Reduced Baloxavir Susceptibility: Impact on Clinical and Virologic Outcomes in Uncomplicated Influenza. J Infect Dis. 2019 Jul 16. pii: jiz244. doi: 10.1093/infdis/jiz244. [Epub ahead of print] PubMed PMID: 31309975.

19: Mishin VP, Patel MC, Chesnokov A, De La Cruz J, Nguyen HT, Lollis L, Hodges E, Jang Y, Barnes J, Uyeki T, Davis CT, Wentworth DE, Gubareva LV. Susceptibility of Influenza A, B, C, and D Viruses to Baloxavir(1). Emerg Infect Dis. 2019 Oct;25(10):1969-1972. doi: 10.3201/eid2510.190607. Epub 2019 Oct 17. PubMed PMID: 31287050; PubMed Central PMCID: PMC6759234.

20: Hussar DA. New Drugs 2019, part 3. Nursing. 2019 Aug;49(8):24-32. doi: 10.1097/01.NURSE.0000569740.20055.9e. PubMed PMID: 31268951.