MAVDA-K-256
MAVDA-K-256 is an orally active SARS-CoV-2 NSP14 inhibitor. MAVDA-K-256 inhibits mRNA cap guanine-N7 methyltransferase by forming an SAH-dependent ternary complex in the viral RNA cap-binding pocket, and inhibits the NSP14 methyltransferases of MERS-CoV, hCoV-229E, and hCoV-NL63 (target IC50 values of ≤ 0.15 nM, 8.4 nM, 5.6 nM, and 2.0 nM, respectively). MAVDA-K-256 exhibits broad-spectrum antiviral activity against alpha- and beta-genus human coronaviruses, is selective over host mRNA cap methyltransferases and unrelated viral or human methyltransferases, reduces lung viral load in mice in a dose-dependent manner, and selects for NSP14 resistance mutations. MAVDA-K-256 can be used for research on SARS-CoV-2 infection.
For research use only. We do not sell to patients.
- Formula: C23H19FN4O4S
- Molecular Weight:466.48
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Huh-7.5 | EC50 |
24.6 nM
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Inhibition of SARS-CoV-2 infection in Huh-7.5 cells.
Inhibition of SARS-CoV-2 infection in Huh-7.5 cells.
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acs.jmedchem.6c01763 |
| Huh-7.5 | CC50 |
10 μM
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Cytotoxicity against Huh-7.5 cells.
Cytotoxicity against Huh-7.5 cells.
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acs.jmedchem.6c01763 |
| Huh-7.5 | EC50 |
0.7 nM
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Inhibition of SARS-CoV-2 infection in Huh-7.5 cells in the presence of 5 μM DZNeP.
Inhibition of SARS-CoV-2 infection in Huh-7.5 cells in the presence of 5 μM DZNeP.
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acs.jmedchem.6c01763 |
| Huh-7.5 | CC50 |
1 μM
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Cytotoxicity against Huh-7.5 cells in the presence of 5 μM DZNeP.
Cytotoxicity against Huh-7.5 cells in the presence of 5 μM DZNeP.
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acs.jmedchem.6c01763 |
| Huh-7.5 | EC50 |
0.72 μM
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Inhibition of hCoV-NL63 infection in Huh-7.5 cells.
Inhibition of hCoV-NL63 infection in Huh-7.5 cells.
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acs.jmedchem.6c01763 |
| Huh-7.5 | EC50 |
1.22 μM
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Inhibition of hCoV-229E infection in Huh-7.5 cells.
Inhibition of hCoV-229E infection in Huh-7.5 cells.
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acs.jmedchem.6c01763 |
| Huh-7.5 | EC50 |
0.20 μM
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Inhibition of hCoV-OC43 infection in Huh-7.5 cells.
Inhibition of hCoV-OC43 infection in Huh-7.5 cells.
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acs.jmedchem.6c01763 |
| Huh-7.5 | CC50 |
30 μM
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Cytotoxicity against Huh-7.5 cells in hCoV infection assays.
Cytotoxicity against Huh-7.5 cells in hCoV infection assays.
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acs.jmedchem.6c01763 |
| Vero E6 | EC50 |
27.3 nM
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Inhibition of SARS-CoV-2 infection in Vero E6 cells after 1 hr compound pre-incubation and 24 hr fixation.
Inhibition of SARS-CoV-2 infection in Vero E6 cells after 1 hr compound pre-incubation and 24 hr fixation.
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acs.jmedchem.6c01763 |
| Vero E6 | EC50 |
10 μM
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Inhibition of SARS-CoV-2 infection in Vero E6 cells after 3 passages under stepwise increasing MAVDA-K-256 concentrations.
Inhibition of SARS-CoV-2 infection in Vero E6 cells after 3 passages under stepwise increasing MAVDA-K-256 concentrations.
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acs.jmedchem.6c01763 |
In Vitro
MAVDA-K-256 (10 μM) inhibits NSP14 of α- and β-hCoVs with IC50 values of 2.0-8.4 nM and shows no activity against selected host or viral MTases[1].
MAVDA-K-256 inhibits SARS-CoV-2 replication in Huh-7.5 cells with an EC50 of 24.6 nM, which is enhanced to 0.7 nM upon inhibition by
Adenosylhomocysteinase (AHCY) (HY-149048)[1].
MAVDA-K-256 shows broad-spectrum cell-level anti-hCoV activity in Huh-7.5 cells, with EC50 values of 0.20-1.22 μM[1].
MAVDA-K-256 (10 μM) does not significantly inhibit major drug-metabolizing CYPs and lacks key time-dependent CYP inhibition[1].
MAVDA-K-256 (10 μM) shows a favorable off-target profile, with weak inhibition of 5-HTT/PDE3A (IC50 > 10 μM) and low inhibition of hERG (IC50 = 24.8 μM)[1].
MAVDA-K-256 (up to 25 μg/mL) shows no mutagenicity in the Mini-Ames TA98/TA100 assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | AUC0-24 | Bioavailability | AUCinf | T1/2 | CLplasma | Vdss |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 5 mg/kg | i.v. | / | / | / | 2.9 h | 0.81 mL/min/kg | 0.2 L/kg |
| Mice[1] | 25 mg/kg | p.o. | 210 μg·h/mL | 39.5 % | 203,009 ng·h/mL | / | / | / |
| Mice[1] | 10 mg/kg | p.o. | 84.4 μg·h/mL | / | / | / | / | / |
| Mice[1] | 50 mg/kg | p.o. | 456 μg·h/mL | / | / | / | / | / |
| Mice[1] | 100 mg/kg | p.o. | 941 μg·h/mL | / | / | / | / | / |
| Rat[1] | 3 mg/kg | i.v. | / | / | / | 5.3 h | 0.33 mL/min/kg | 0.15 L/kg |
| Rat[1] | 10 mg/kg | p.o. | / | 47.2 % | / | / | / | / |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:K18-hACE2 (transgenic)[1]
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Dosage:10, 30, and 100 mg/kg
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Administration:p.o.; BID; from 12 h post-infection until day 3
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Result:Reduced SARS-CoV-2 lung viral titers by 3.0, 4.1, and 5.5 orders of magnitude at 10, 30, and 100 mg/kg, respectively.
Chemical Information
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Molecular Weight 466.48
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Formula C23H19FN4O4S
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SMILES
CC1=CC2=C(C=N1)OC(C3=C(C=C(C=C3)NS(C4=CC5=C(C=C4F)N(C(C5)=O)C)(=O)=O)C)=N2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MAVDA-K-256 Related Classifications
HY-191055 Related Classifications
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