PAV-104
Based on 1 Customer Validation
PAV-104 (MAV-104) is a host-targeted, pan-respiratory viral assembly inhibitor. PAV-104 targets a small subset of the host protein 14-3-3 within a transient multi-protein complex. PAV-104 inhibits SARS-CoV-2 replication by blocking post-entry viral assembly/budding through interaction with viral nucleocapsid (N) protein and interference with its oligomerization. PAV-104 is orally active in cats and shows favorable pharmacokinetic properties in rats. PAV-104 can be used for the study of COVID-19 and other respiratory viral infections, including Feline Infectious Peritonitis (FIP).
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- Purity: 99.83%
- CAS No.: 2923674-83-1
- 화학식: C29H35N5O6S
- 분자량:581.68
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| AEC | Inhibition |
> 99 %
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Achieves >99% inhibition of SARS-CoV-2 Gamma variant replication in primary AECs at 100 nM.
Achieves >99% inhibition of SARS-CoV-2 Gamma variant replication in primary AECs at 100 nM.
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38649430 |
| Calu-3 | CC50 |
3732 nM
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Shows cytotoxicity in Calu-3 cells.
Shows cytotoxicity in Calu-3 cells.
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38649430 |
| Calu-3 | EC90 |
23.5 nM
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Inhibits SARS-CoV-2 replication in Calu-3 cells.
Inhibits SARS-CoV-2 replication in Calu-3 cells.
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38649430 |
In Vitro
PAV-104 (MAV-104) (0-5000 nM; 48 h) shows a CC50 of 3732 nM in Calu-3 cells[1].
PAV-104 (6.25-100 nM; 1 h preincubation; 24 h post-infection) dose-dependently inhibits SARS-CoV-2 replication and suppresses infectious virus release in supernatants of SARS-CoV-2-infected Calu-3 cells[1].
PAV-104 (6.25-100 nM; 1 h preincubation; 72 h post-infection) reduces SARS-CoV-2-infected Calu-3 cells[1].
PAV-104 (0.001-1000 nM; 1 h preincubation; 48 h post-infection) inhibits SARS-CoV-2 replication in Calu-3 cells (EC50 = 1.7 nM, EC90 = 23.5 nM) and suppresses infectious SARS-CoV-2 titers in cell supernatants (EC50 = 0.5 nM, EC90 = 10.3 nM)[1].
PAV-104 (100 nM; 36 h post-infection) suppresses SARS-CoV-2 Gamma variant replication in primary human airway epithelial cells (AECs) (achieving > 99% inhibition at the tested concentration), and reduces SARS-CoV-2 Delta and Omicron variant replication in air–liquid interface (ALI) cultured primary AECs[1].
PAV-104 (50 nM; 1 h pre-infection treatment) does not inhibit SARS-CoV-2 release into supernatants at 24 h post-infection[1].
PAV-104 (50 nM; 20 min post-entry treatment; 24 h incubation) reduces SARS-CoV-2 viral titers in Calu-3 cell supernatants[1].
PAV-104 (100 nM; post-entry treatment; 36 h incubation) reduces SARS-CoV-2 N gene expression in primary AECs at ALI culture compared to pre-infection treatment[1].
PAV-104 (6.25-100 nM; 60 h) dose-dependently reduces SARS-CoV-2 structural proteins (N, M, E, S) in ultracentrifuged pellets of VLP-producing HEK293T cell supernatants, and does not affect protein synthesis or steady-state actin levels in cell lysates[1].
PAV-104 (0-100 nM; 60 h) inhibits SARS-CoV-2 virus-like particle (VLP) production in HEK293T cells transfected with N, M, E, and S proteins in a dose-dependent manner and has no effect on extracellular vesicle secretion from empty vector-transfected cells[1].
PAV-104 (50 nM; 2 h entry; 18 h post-entry incubation) in single-cycle infectious SARS-CoV-2 ΔS-VRP-infected Calu-3 cells does not affect N mRNA levels or N protein synthesis, but inhibits viral particle release into supernatants[1].
PAV-104 (cell extracts incubated for 1 h; eluted with free drug for 2 h) binds directly to SARS-CoV-2 N protein in Calu-3 cell extracts (Delta and Omicron variants)[1].
PAV-104 (20 h ultracentrifugation) inhibits the oligomerization of SARS-CoV-2 N protein in N-transfected HEK293T cells, and shows a reduction in the N intermediate complex (Fractions 20-22) in glycerol gradient ultracentrifugation[1].
PAV-104 (100 nM; 36 h post-infection) in SARS-CoV-2-infected primary AECs reverses SARS-CoV-2 induction of type-I interferon response and the maturation of nucleoprotein signaling pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Calu-3 cells
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Concentration:0-5000 nM
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Incubation Time:48 h
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Result:Shows a CC50 of 3732 nM.
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Cell Line:Calu-3 cells
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Concentration:6.25, 25, 50, 100 nM
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Incubation Time:1 h preincubation + 24 h infection
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Result:Dose-dependently inhibited SARS-CoV-2 replication.
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Cell Line:Calu-3 cells
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Concentration:6.25-100 nM
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Incubation Time:1 h preincubation + 72 h infection
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Result:Reduced SARS-CoV-2-infected Calu-3 cells.
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Cell Line:Calu-3 cells
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Concentration:0.001-1000 nM
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Incubation Time:1 h preincubation + 48 h infection
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Result:Inhibited SARS-CoV-2 replication in Calu-3 cells (EC50 = 1.7 nM, EC90 = 23.5 nM).
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Cell Line:HEK-293T cells (transfected with N, M, E, S)
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Concentration:6.25-100 nM
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Incubation Time:60 h
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Result:Dose-dependently reduced SARS-CoV-2 structural proteins (N, M, E, S) in ultracentrifuged pellets of VLP-producing HEK-293T cell supernatants.
Did not affect protein synthesis or steady-state actin levels in cell lysates.
Parmacokinetics
| Species | Dose | Route | AUClast | Tmax | Cmax | AUCINF_obs | MRTlast | MRTINF_obs | AUC0-inf | T1/2 | F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Cat[3] | 3.2 mg/kg | p.o. | 1345.438 ng/mL·h | 2 h | 93.21667 ng/mL | 1456.63 ng/mL·h | 9.178434 h | 10.94357 h | / | / | / |
| Rat[2] | 20 mg/kg | p.o. | 1099 nM·h | 0.5 h | 479 nM | / | / | / | 1225 nM·h | 9 h | 32 % |
| Rat[2] | 5 mg/kg | i.p. | 849 nM·h | 0.25 h | 759 nM | / | / | / | 899 nM·h | 7 h | 95 % |
In Vivo
PAV-104 (200-3200 μg/kg; p.o.; single escalating dose) in domestic shorthair cats (3 males, 3 females, 50.5-56.0 months old) is well tolerated with no adverse effects observed at any dose, and reaches plasma concentrations exceeding the anti-coronavirus EC50 (1.725 nM) at all doses tested and EC90 (24.5 nM) at doses above 400 μg/kg[3].
PAV-104 (800 and 3200 μg/kg; p.o.; once daily for 15 days) in domestic shorthair cats (9 males, 9 females, 6 months to 9 years old) is well tolerated, with adverse events (vomiting, decreased appetite, hypersalivation) observed across all groups including vehicle control, all resolving during the study[3].
PAV-104 (800 and 3200 μg/kg; p.o.; once daily for 14 days) in domestic shorthair cats shows higher plasma concentrations after 14 days of daily administration compared to a single dose[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Dose-escalation safety study in Domestic shorthair cats (3M/3F, 50.5-56.0 mo) [3]
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Dosage:200, 400, 800, 1600, 3200 μg/kg
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Administration:p.o.; single escalating dose
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Result:No adverse effects; plasma concentrations exceeded EC50 at all doses, EC90 above 400 μg/kg Showed no adverse effects observed at any dose.
Reached plasma concentrations exceeding the anti-coronavirus EC50 (1.725 nM) at all doses tested and EC90 (24.5 nM) at doses above 400 μg/kg.
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Animal Model:Repeat-dose safety study in Domestic shorthair cats (9M/9F, 6 mo-9 yr) [3]
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Dosage:800, 3200 μg/kg
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Administration:p.o.; once daily for 14-15 days
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Result:Showed a well tolerance, with adverse events (vomiting, decreased appetite, hypersalivation) observed across all groups including vehicle control, all resolving during the study (15 days).
Exhibited higher plasma concentrations after 14 days of daily administration compared to a single dose.
Chemical Information
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CAS No. 2923674-83-1
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Appearance Solid
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분자량 581.68
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화학식 C29H35N5O6S
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Color White to light yellow
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SMILES
COC1=C(C=CC=C1CNC(C2=CC(C3CC3)=NN2C)=O)OCC4=CC=C(C=C4)C(N5CCN(CC5)S(C)(=O)=O)=O
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Synonyms
MAV-104
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : 100 mg/mL (171.92 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
순도&문서
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Data Sheet (280 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Du L, et al. A viral assembly inhibitor blocks SARS-CoV-2 replication in airway epithelial cells. Commun Biol. 2024 Apr 22;7(1):486. [Content Brief]
[2]. Michon M, et al. A pan-respiratory antiviral chemotype targeting a transient host multi-protein complex. Open Biol. 2024 Jun;14(6):230363. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.7192 mL | 8.5958 mL | 17.1916 mL | 42.9790 mL |
| 5 mM | 0.3438 mL | 1.7192 mL | 3.4383 mL | 8.5958 mL | |
| 10 mM | 0.1719 mL | 0.8596 mL | 1.7192 mL | 4.2979 mL | |
| 15 mM | 0.1146 mL | 0.5731 mL | 1.1461 mL | 2.8653 mL | |
| 20 mM | 0.0860 mL | 0.4298 mL | 0.8596 mL | 2.1489 mL | |
| 25 mM | 0.0688 mL | 0.3438 mL | 0.6877 mL | 1.7192 mL | |
| 30 mM | 0.0573 mL | 0.2865 mL | 0.5731 mL | 1.4326 mL | |
| 40 mM | 0.0430 mL | 0.2149 mL | 0.4298 mL | 1.0745 mL | |
| 50 mM | 0.0344 mL | 0.1719 mL | 0.3438 mL | 0.8596 mL | |
| 60 mM | 0.0287 mL | 0.1433 mL | 0.2865 mL | 0.7163 mL | |
| 80 mM | 0.0215 mL | 0.1074 mL | 0.2149 mL | 0.5372 mL | |
| 100 mM | 0.0172 mL | 0.0860 mL | 0.1719 mL | 0.4298 mL |
PAV-104 Related Classifications
HY-158405 Related Classifications
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