Baloxavir

Baloxavir is a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit.

Product information

CAS Number: 1985605-59-1

Molecular Weight: 483.49

Formula: C24H19F2N3O4S

Synonym:

Baloxavir acid

BXA

S-033447

Chemical Name: (R)-12-((S)-7, 8-difluoro-6, 11-dihydrodibenzo[b, e]thiepin-11-yl)-7-hydroxy-3, 4, 12, 12a-tetrahydro-1H-[1, 4]oxazino[3, 4-c]pyrido[2, 1-f][1, 2, 4]triazine-6, 8-dione

Smiles: OC1=C2C(=O)N3CCOC[C@H]3N([C@H]3C4=CC=C(F)C(F)=C4CSC4=CC=CC=C43)N2C=CC1=O

InChiKey: FIDLLEYNNRGVFR-CTNGQTDRSA-N

InChi: 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

Technical Data

Appearance: Solid Power

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

Solubility: DMSO: 47 mg/mL (97.21mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

BXA (baloxavir acid) inhibited viral RNA transcription via selective inhibition of CEN activity in enzymatic assays, and inhibited viral replication in infected cells without cytotoxicity in cytopathic effect assays. The antiviral activity of BXA was also confirmed in yield reduction assays with seasonal type A and B viruses, including neuraminidase inhibitor-resistant strains. Furthermore, BXA showed broad potency against various subtypes of influenza A viruses (H1N2, H5N1, H5N2, H5N6, H7N9 and H9N2). Additionally, serial passages of the viruses in the presence of BXA resulted in isolation of PA/I38T variants with reduced BXA susceptibility. Phenotypic and genotypic analyses with reverse genetics demonstratde the mechanism of BXA action via CEN inhibition in infected cells. These results revealed the in vitro characteristics of BXA and support clinical use of BXM to treat influenza.

In Vivo:

In order to evaluate the effects of BXM (baloxavir marboxil) against A(H7N9) in a lethal infection model, mice were inoculated with 10.4 times of 50% mouse lethal dose (MLD50) of A/Anhui/1/2013 (H7N9). All vehicle-treated mice died within 7 days post-infection (dpi) and mean day to death was 6 days (Fig. 1a). Survival rates of BXM at 0.5, 5, and 50 mg/kg twice a day for 1 day were 90%, 100% and 100%, respectively. When compared to the survival time at 28 dpi, all groups treated with BXM showed significant prolonged survival times compared with the groups administered with vehicle. Dramatic body weight loss after infection was observed in the vehicle-treated control group and reached a 28% decrease at 5 dpi (Fig. 1b and Supplementary Fig. 2). By contrast, BXM significantly prevented body weight loss from day 2 to 5 in a dose-dependent manner. These results indicate that BXM exerts improvements in survival in mice infected with A/Anhui/1/2013 (H7N9).

References:

1. Koshimichi H, Ishibashi T, Wajima T. Population Pharmacokinetics of Baloxavir Marboxil in Japanese Pediatric Influenza Patients. J Pharm Sci. 2019 Apr 15. pii: S0022-3549(19)30236-9.
2. LaVoie EJ, Sagong HY, Bauman JD, Nogales A, Martínez-Sobrido L, Arnold E. Aryl and arylalkyl substituted 3-hydroxypyridin(1H)-2-ones: Synthesis and evaluation as inhibitors of influenza A endonuclease. ChemMedChem. 2019 Apr 14.
3. Beigel JH, Nam HH, Adams PL, Krafft A, Ince WL, El-Kamary SS, Sims AC. Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference. Antiviral Res. 2019 Apr 8;167:45-67.

Products are for research use only. Not for human use.