ML336
Based on 1 Customer Validation
ML336 is a Venezuelan equine encephalitis virus (VEEV) inhibitor with moderate passive blood-brain barrier permeability. ML336 inhibits viral RNA synthesis, virus-induced cytopathic effects and viral replication, reduces viral titers, and blocks the synthesis of VEEV genomic, subgenomic and template RNAs. ML336 can be used in studies related to VEEV infection.
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- Purity: 99.65%
- CAS No.: 1613465-33-0
- 화학식: C19H21N5O3
- 분자량:367.40
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
Biological Activity
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| Vero 76 | CC50 |
>50 μM
Compound: 45, ML336
|
Cytotoxicity against african green monkey Vero 76 cells after 3 days by Celltiter-Glo reagent based assay
Cytotoxicity against african green monkey Vero 76 cells after 3 days by Celltiter-Glo reagent based assay
|
[PMID: 25244572] |
| Vero 76 | EC50 |
>50 μM
Compound: 45, ML336
|
Antiviral activity against Venezuelan equine encephalitis virus TC83 containing non-structural protein 4 Q210K mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
Antiviral activity against Venezuelan equine encephalitis virus TC83 containing non-structural protein 4 Q210K mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
|
[PMID: 25244572] |
| Vero 76 | EC50 |
0.02 μM
Compound: 45, ML336
|
Antiviral activity against Venezuelan equine encephalitis virus V3526 infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
Antiviral activity against Venezuelan equine encephalitis virus V3526 infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
|
[PMID: 25244572] |
| Vero 76 | EC50 |
0.03 μM
Compound: 45, ML336
|
Antiviral activity against Venezuelan equine encephalitis virus TC83 infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
Antiviral activity against Venezuelan equine encephalitis virus TC83 infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
|
[PMID: 25244572] |
| Vero 76 | EC50 |
0.04 μM
Compound: 45, ML336
|
Antiviral activity against Venezuelan equine encephalitis virus TrD infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
Antiviral activity against Venezuelan equine encephalitis virus TrD infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
|
[PMID: 25244572] |
| Vero 76 | EC50 |
0.17 μM
Compound: 45, ML336
|
Antiviral activity against Venezuelan equine encephalitis virus TC83 infected in Vero 76 cells assessed as reduction in viral titer by crystal violet staining based microplaque assay relative to untreated control
Antiviral activity against Venezuelan equine encephalitis virus TC83 infected in Vero 76 cells assessed as reduction in viral titer by crystal violet staining based microplaque assay relative to untreated control
|
[PMID: 25244572] |
| Vero 76 | EC50 |
17 μM
Compound: 45, ML336
|
Antiviral activity against Venezuelan equine encephalitis virus TC83 containing non-structural protein 2 Y102C mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
Antiviral activity against Venezuelan equine encephalitis virus TC83 containing non-structural protein 2 Y102C mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
|
[PMID: 25244572] |
| Vero 76 | EC50 |
19 μM
Compound: 45, ML336
|
Antiviral activity against Venezuelan equine encephalitis virus TC83 containing non-structural protein 2 D116N mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
Antiviral activity against Venezuelan equine encephalitis virus TC83 containing non-structural protein 2 D116N mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
|
[PMID: 25244572] |
| Vero 76 | EC50 |
19 μM
Compound: 45, ML336
|
Antiviral activity against Venezuelan equine encephalitis virus V3526 containing non-structural protein 2 Y102C mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
Antiviral activity against Venezuelan equine encephalitis virus V3526 containing non-structural protein 2 Y102C mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
|
[PMID: 25244572] |
| Vero 76 | EC50 |
66 μM
Compound: 45, ML336
|
Antiviral activity against Venezuelan equine encephalitis virus V3526 containing non-structural protein 4 Q210K mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
Antiviral activity against Venezuelan equine encephalitis virus V3526 containing non-structural protein 4 Q210K mutant infected in Vero 76 cells assessed as reduction in virus-induced cytopathic effect after 2 days by Celltiter-Glo reagent based assay
|
[PMID: 25244572] |
ML336 (48 h) potently inhibits the cytopathic effect induced by VEEV TC-83 in Vero 76 cells, with an EC50 of 0.03 μM[1].
ML336 (48 h) potently inhibits the cytopathic effect induced by VEEV V3526 in Vero 76 cells, with an EC50 of 0.02 μM[1].
ML336 (48 h) potently inhibits the cytopathic effect induced by VEEV TrD in Vero 76 cells, with an EC50 of 0.04 μM[1].
ML336 (0.5-5 μM; 40 h) potently reduces the viral titer of VEEV TC-83 in Vero 76 cells, leading to a > 7.2 log decrease in viral titer at a concentration of 1 μM, with an EC90 of 0.17 μM[1].
ML336 (0.5-5 μM; 40 h) completely blocks detectable VEEV TrD viral replication in Vero 76 cells at concentrations as low as 0.5 μM[1].
The potency of ML336 (48 h) is significantly reduced against VEEV strains with mutations in nsP2 or nsP4, indicating that it inhibits viral replication by targeting viral non-structural proteins 2 and/or 4[1].
ML336 (48 h) potently protects Vero 76 cells against the cytopathic effect (CPE) induced by VEEV TC-83, with an EC50 of 32 nM, and reduces viral titers by more than 7.2 log orders at a concentration of 5 μM[2].
ML336 (0.00001-1000 nM; 2 h) potently and dose-dependently inhibits VEEV TC-83 RNA synthesis in BHK21 cells, with an IC50 of 1.1 nM; it reduces the synthesis level to 7% of that in the control group at a concentration of 40 nM, and completely blocks the synthesis of the parental V3526 strain at 5 μM[2].
ML336 (5 μM) inhibits the RNA synthesis of both positive-sense and negative-sense VEEV TC-83 in BHK21 cells, and prevents any increase in viral RNA copy numbers during 4 to 6 HPI at a concentration of 5 μM[2].
ML336 (5 μM; 2 h) inhibits positive-strand VEEV TC-83 RNA synthesis mediated by mature replicase complexes in BHK21 cells; even when translation (and negative-strand RNA synthesis) is inhibited by cycloheximide, 5 μM of this compound still completely blocks RNA production[2].
ML336 (2.5 μM; 2 h) inhibits the synthesis of genomic (49S) and subgenomic (26S) VEEV TC-83 RNA in BHK21 cells, and completely abolishes the production of both RNAs when added at a concentration of 2.5 μM at any time within 8 hours post-infection (HPI)[2].
ML336 (0.32-1000 nM; 90 min) directly inhibits RNA synthesis of VEEV TC-83 in a cell-free system by interacting with the viral replicase complex, with an IC50 of 49 nM, and completely blocks the synthesis at concentrations ≥ 200 nM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:BHK21 cells
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Concentration:5 μM
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Incubation Time:treated at 4 HPI, sampled at 4, 5, 6 HPI
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Result:Prevented any increase in positive-sense or negative-sense viral RNA over the period between 4 and 6 HPI.
Maintained the ratio of positive to negative-sense RNA at 10,000:1, consistent with untreated cells.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C3H/HeN (5- to 6-week-old; intranasal challenge with 10× LD50 of VEEV TC-83 strain)[1]
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Dosage:2.5 mg/kg (twice daily, total daily dose 5 mg/kg)
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Administration:i.p.; twice daily; 4 days
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Result:Conferred 71% survival rate at day 21.
Chemical Information
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CAS No. 1613465-33-0
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Appearance Solid
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분자량 367.40
-
화학식 C19H21N5O3
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Color Off-white to yellow
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SMILES
O=C(NC1=CC=CC=C1)C2=CC([N+]([O-])=O)=CC=C2/N=C3N(C)CCN(C)C/3
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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
DMSO : 20 mg/mL (54.44 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 (278 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
References
[1]. Schroeder CE, et al. Development of (E)-2-((1,4-dimethylpiperazin-2-ylidene)amino)-5-nitro-N-phenylbenzamide, ML336: Novel 2-amidinophenylbenzamides as potent inhibitors of venezuelan equine encephalitis virus. Journal of medicinal chemistry. 2014 Oct 23;57(20):8608-21. [Content Brief]
[2]. Skidmore AM, et al. Benzamidine ML336 inhibits plus and minus strand RNA synthesis of Venezuelan equine encephalitis virus without affecting host RNA production. Antiviral research. 2020 Feb;174:104674. [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 | 2.7218 mL | 13.6091 mL | 27.2183 mL | 68.0457 mL |
| 5 mM | 0.5444 mL | 2.7218 mL | 5.4437 mL | 13.6091 mL | |
| 10 mM | 0.2722 mL | 1.3609 mL | 2.7218 mL | 6.8046 mL | |
| 15 mM | 0.1815 mL | 0.9073 mL | 1.8146 mL | 4.5364 mL | |
| 20 mM | 0.1361 mL | 0.6805 mL | 1.3609 mL | 3.4023 mL | |
| 25 mM | 0.1089 mL | 0.5444 mL | 1.0887 mL | 2.7218 mL | |
| 30 mM | 0.0907 mL | 0.4536 mL | 0.9073 mL | 2.2682 mL | |
| 40 mM | 0.0680 mL | 0.3402 mL | 0.6805 mL | 1.7011 mL | |
| 50 mM | 0.0544 mL | 0.2722 mL | 0.5444 mL | 1.3609 mL |