AVI8122
AVI8122 is a covalent coronavirus main protease (Mpro) inhibitor, with IC50 values of 0.0047 μM, 0.065 μM, 0.04 μM, 0.004 μM, 0.027 μM and 0.020 μM against SARS-CoV-2, MERS-CoV, HKU8, PEDV, IBV and HKU15, respectively; it exhibits Ki values of 0.14 nM, 1.8 nM, 0.9 nM, 0.2 nM and 5.2 nM against SARS-CoV-2, HKU8, PEDV, IBV and HKU15, respectively. AVI8122 forms a covalent hemithioacetal bond with the catalytic cysteine of Mpro, blocks its proteolytic activity, and acts on the four coronavirus genera α, β, γ and δ. AVI8122 is applicable to research related to SARS-CoV-2 infection.\n
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C24H29FN4O5
- 分子量:472.51
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保管条件:
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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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
IC50 & Target
[1]|
SARS-CoV-2 Mpro 4.7 nM (IC50) |
SARS-CoV-2 Mpro 0.14 nM (Ki) |
MERS-CoV Mpro 65 nM (IC50) |
HKU8 Mpro 40 nM (IC50) |
HKU8 Mpro 1.8 nM (Ki) |
PEDV Mpro 4 nM (IC50) |
PEDV Mpro 0.9 nM (Ki) |
IBV Mpro 27 nM (IC50) |
IBV Mpro 0.2 nM (Ki) |
HKU15 Mpro 20 nM (IC50) |
HKU15 Mpro 5.2 nM (Ki) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | EC50 |
3.1 μM
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Inhibition of SARS-CoV-2 Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
Inhibition of SARS-CoV-2 Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
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42461134 |
| HEK293 | EC50 |
1.5 μM
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Inhibition of MERS-CoV Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
Inhibition of MERS-CoV Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
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42461134 |
| HEK293 | EC50 |
1.1 μM
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Inhibition of PEDV Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
Inhibition of PEDV Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
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42461134 |
| HEK293 | EC50 |
3.6 μM
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Inhibition of HKU8 Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
Inhibition of HKU8 Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
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42461134 |
| HEK293 | EC50 |
13 μM
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Inhibition of IBV Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
Inhibition of IBV Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
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42461134 |
| HEK293 | EC50 |
4 μM
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Inhibition of HKU15 Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
Inhibition of HKU15 Mpro activity in human HEK 293 cells transfected with a luciferase-linked Mpro reporter system, incubated for 24 h post-treatment, measured via luminescence readout.
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42461134 |
| A549 | EC50 |
37 μM
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Inhibited WT SARS-CoV-2 replication.
Inhibited WT SARS-CoV-2 replication.
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42461134 |
| A549 | EC50 |
74 μM
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Inhibited SARS-CoV-2 Alpha variant replication.
Inhibited SARS-CoV-2 Alpha variant replication.
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42461134 |
| A549 | EC50 |
98 μM
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Inhibited SARS-CoV-2 Beta variant replication.
Inhibited SARS-CoV-2 Beta variant replication.
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42461134 |
| A549 | EC50 |
68 μM
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Inhibited SARS-CoV-2 Gamma variant replication.
Inhibited SARS-CoV-2 Gamma variant replication.
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42461134 |
| A549 | EC50 |
102 μM
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Inhibited SARS-CoV-2 Delta variant replication.
Inhibited SARS-CoV-2 Delta variant replication.
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42461134 |
| Vero E6 | EC50 |
2.6 μM
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Inhibited SARS-CoV-2 Omicron variant replication.
Inhibited SARS-CoV-2 Omicron variant replication.
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42461134 |
体外実験
AVI8122 (0-100 μM; 10 min at 37 °C) potently inhibits the Mpro enzymatic activity of various coronaviruses, including SARS-CoV-2 (IC50 = 0.0047 μM), MERS-CoV, HKU8, PEDV, IBV, HKU15, and human common cold coronaviruses, with its potency consistently ranging from sub-20 nM to low micromolar levels[1].
AVI8122 (0-0.4 μM) is a tight-binding inhibitor of Mpro from SARS-CoV-2, PEDV, HKU8, IBV and HKU15, with a Ki of 0.14 nM; all Ki values fall within the low nanomolar range[1].
AVI8122 (20 μM; 10 min at room temperature; dialyzed for up to 80 h) forms a practically irreversible complex with SARS-CoV-2 Mpro, whereas its binding to IBV Mpro and HKU8 Mpro is partially reversible, with species-dependent residence times[1].
AVI8122 potently inhibits the replication of wild-type SARS-CoV-2 in A549-ACE2-TMPRSS2 cells (EC50 = 36.9 nM), while also suppressing the replication of its variants of concern; when P-glycoprotein efflux is inhibited, the potency of this drug against the Omicron variant in Vero E6 cells is further enhanced[1].
AVI8122 (0.02-400 μM; 24 h) inhibits the Mpro activity of SARS-CoV-2, MERS-CoV, PEDV, HKU8, IBV and HKU15 in HEK 293 cells, with an EC50 of 3.1 μM against SARS-CoV-2, and its cytotoxicity is low relative to its antiviral potency[1].
AVI8122 (0.1 nM-2 mM; 10 min at 37 °C) exhibits weak inhibitory activity against human cathepsin S, cathepsin B, and cathepsin L, with high selectivity over SARS-CoV-2 Mpro (selectivity index of 280-700)[1].
AVI8122 exhibits favorable in vitro pharmacokinetic properties, including high metabolic stability in human liver microsomes and hepatocytes, moderate plasma protein binding in humans, high solubility, and a moderate LogD value[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
体内実験
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:B6.Cg-Tg(K18-ACE2)2Prlmn/J (K18-hACE2) (male, 5 weeks old, intranasal challenge with 5000 PFU of WT SARS-CoV-2)[1]
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Dosage:20 mg/kg; 100 mg/kg
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Administration:i.p.; twice daily; 5 days (20 mg/kg, 100 mg/kg non-survival); i.p.; twice daily; 8 days (100 mg/kg survival)
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Result:Prevented weight loss in 100 mg/kg group, while vehicle and 20 mg/kg groups showed significant weight loss by day 5.
Achieved an 80% survival rate (4/5 mice) in 100 mg/kg group, while all mice in vehicle and 20 mg/kg groups were euthanized by day 5.
Reduced lung tissue infectious viral titers to 104.4 PFU/mL in 20 mg/kg group and 104.7 PFU/mL in 100 mg/kg group at day 5; eliminated detectable infectious virus in lung tissue of 100 mg/kg survival group at day 14.
Significantly reduced lung tissue viral RNA in 100 mg/kg group relative to vehicle controls at day 14.
Reduced respiratory swab viral RNA to 104.8 copies/mL in 100 mg/kg group at day 14, significantly lower than vehicle group's 107.2 copies/mL.
Significantly reduced lung injury (ATS ALI scores) in 100 mg/kg group at both day 5 and day 14, with near-complete restoration of healthy lung morphology by day 14.
化学情報
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分子量 472.51
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分子式 C24H29FN4O5
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SMILES
O=C1[C@H](C[C@H](NC([C@@H](NC(C2=CC(C=CC=C3F)=C3N2)=O)CC4CC4)=O)C(CO)=O)CCCN1
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
AVI8122 関連分類
HY-187507 関連分類
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