Bemnifosbuvir Hemisulfate (AT-527)

Catalog No.E1013 Batch:E101301

Technical Data

Formula	C₂₄H₃₃FN₇O₇P._1/2H₂O₄S
Molecular Weight	630.55	CAS No.	2241337-84-6
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (158.59 mM)
		Water	100 mg/mL (158.59 mM)
		Ethanol	100 mg/mL (158.59 mM)
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

Bemnifosbuvir Hemisulfate (AT-527, RG-6422, RO 7496998) is a hemi-sulfate salt of AT-511. AT-511 is a potent inhibitor of SARS-CoV-2 with an EC90 of 0.47 μM.

Targets

SARS-CoV-2 ^[1]

0.47 μM(EC90)

In vitro

AT-511 is the free base of AT-527. AT-511 inhibits replication of several human coronaviruses, such as HCoV-229E, HCoV-OC43, SARS-CoV in Huh-7 cells and HCoV-229E in BHK-21 cells. AT-511 can also inhibits SARS-CoV-2 replication in primary human airway epithelial (HAE) cells. In HBE and HNE cells, AT-511 can promote the host cells to form the pharmacologically active TP, AT-9010, to inhibit virus replication.^[1]

In vivo

In nonhuman primates (NHPs), after oral administration of AT-527, T-273 has the longest MRT at all dose levels, which indicate the long half-life of the active TP formed intracellularly. AT-527 is preferentially delivered to the liver, the target organ for HCV infection.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Huh-7, BHK-21, HBE, HNE cells Concentrations 100 μM, 20 μM, 4 μM, 0.8 μM Incubation Time 2h, 8 h, 3 days Method AT-511 dilution is added to 5 wells of a 96-well plate with 80 to 100% confluent cells. Three wells of each dilution are infected with virus, and two wells remain uninfected as toxicity controls. Six untreated wells are infected as virus controls, and six untreated wells are left uninfected to use as virus controls. Viruses are diluted to achieve MOIs of 0.003, 0.002, 0.001, and 0.03 CCID50 (50% cell culture infectious dose) per cell for 229E, OC43, MERS, and SARS coronaviruses, respectively.Plates are incubated at 37°C in a humidified atmosphere containing 5% CO2.The plates are stained with neutral red dye for approximately 2 h (±15 min). Supernatant dye was removed, wells are rinsed with phosphate-buffered saline (PBS), and the incorporated dye is extracted in 50:50 Sorensen citrate buffer-ethanol for >30 min. The optical density is read on a spectrophotometer at 540 nm and converts to percentage of controls.
Animal Study:^{^[1]}	Animal Models Male nonnaive cynomolgus monkeys Dosages 60 mg/kg, 30mg/kg Administration p.o.

Cell Assay:^{^[1]}

Cell lines
Huh-7, BHK-21, HBE, HNE cells
Concentrations
100 μM, 20 μM, 4 μM, 0.8 μM
Incubation Time
2h, 8 h, 3 days
Method
AT-511 dilution is added to 5 wells of a 96-well plate with 80 to 100% confluent cells. Three wells of each dilution are infected with virus, and two wells remain uninfected as toxicity controls. Six untreated wells are infected as virus controls, and six untreated wells are left uninfected to use as virus controls. Viruses are diluted to achieve MOIs of 0.003, 0.002, 0.001, and 0.03 CCID50 (50% cell culture infectious dose) per cell for 229E, OC43, MERS, and SARS coronaviruses, respectively.Plates are incubated at 37°C in a humidified atmosphere containing 5% CO2.The plates are stained with neutral red dye for approximately 2 h (±15 min). Supernatant dye was removed, wells are rinsed with phosphate-buffered saline (PBS), and the incorporated dye is extracted in 50:50 Sorensen citrate buffer-ethanol for >30 min. The optical density is read on a spectrophotometer at 540 nm and converts to percentage of controls.

Animal Study:^{^[1]}

Animal Models
Male nonnaive cynomolgus monkeys
Dosages
60 mg/kg, 30mg/kg
Administration
p.o.

References

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.