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| Targets |
West Nile Virus (WNV) NS2B-NS3 proteinase (IC50 = 0.105 μM) [1]
SID-852843 targets the West Nile Virus NS2B-NS3 proteinase. This viral protease is essential for the replication of the virus, as it processes the viral polyprotein into functional proteins. By inhibiting this enzyme, SID-852843 blocks a critical step in the viral life cycle, thereby preventing virus propagation. The compound's selectivity for the WNV protease over the Dengue virus protease suggests a specific interaction with the WNV enzyme's active site, making it a useful probe for studying flaviviral protease structure and function. |
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| ln Vitro |
SID-852843 has an IC50 value of 0.105 μM, which is sufficient to block WNV NS2B-NS3 protease activity[1].
The compound is a pyrazole ester derivative identified as an allosteric inhibitor of West Nile Virus NS2B-NS3 proteinase via high-throughput screening. [1] It exhibited potent inhibitory activity with an IC50 of 0.105 μM. [1] However, this compound is rapidly hydrolyzed in aqueous buffer (pH = 8) to the corresponding pyrazol-3-ol, with a half-life of approximately 1-2 hours. [1] The hydrolysis product (pyrazol-3-ol) is inactive as an inhibitor of WNV NS2B-NS3 proteinase (IC50 > 100 μM). [1] In vitro, SID-852843 demonstrates potent inhibitory activity against the West Nile Virus NS2B-NS3 protease. Its activity is quantified in a fluorescence-based assay, where it shows a potent IC50 value of 105.0 nM (0.105 μM). This in vitro activity confirms the compound's efficacy in blocking the enzymatic function of the viral target. The inhibition is reversible, indicating non-covalent binding to the enzyme. The compound's potent in vitro activity makes it a promising lead for further antiviral development. |
| ln Vivo |
SID-852843 has demonstrated inhibitory activity against a variety of other biological targets, though with varying potencies. However, its primary and most potent in vitro activity is against the WNV NS2B-NS3 protease. In vivo activity data for this compound are not extensively detailed in standard research summaries. As a protease inhibitor, its potential in vivo efficacy would depend on factors such as bioavailability, metabolic stability, and ability to reach the site of viral replication. The compound is primarily used in in vitro studies to investigate viral protease inhibition.
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| Enzyme Assay |
The assay for WNV NS2B-NS3 protease activity was performed in 10 mM Tris-HCl buffer, pH 8.0, containing 20% (v/v) glycerol and 0.005% Brij 35. The substrate used was Pyr-RTKR-AMC fluorogenic substrate at a concentration of 25 μM, and the enzyme concentration was 10 nM. The total assay volume was 0.1 mL. Initial reaction velocities were monitored continuously at an excitation wavelength of 360 nm and an emission wavelength of 465 nm on a fluorescence spectrophotometer. All assays were performed in triplicate in wells of a 96-well plate. The IC50 values were derived from the assay. The compound SID-852843 was tested in this assay and showed an IC50 of 0.105 μM. [1]
In vitro enzyme assays for SID-852843 are conducted using a fluorescence-based protocol to measure the inhibition of WNV NS2B-NS3 protease activity. The assay typically involves incubating the recombinant protease with a fluorogenic peptide substrate that mimics the viral polyprotein cleavage site. Cleavage of the substrate by the protease releases a fluorescent signal, which is monitored over time. Various concentrations of SID-852843 are added to the reaction mixture, and the decrease in fluorescence is measured to determine the inhibitory effect. The IC50 value of 105.0 nM is calculated from the dose-response curve. |
| Cell Assay |
SID-852843 is primarily evaluated in biochemical enzyme assays rather than complex cell-based assays, as its primary activity is direct protease inhibition. In vitro cellular assays would typically involve treating virus-infected cell cultures with the compound and measuring the reduction in viral replication. This could be done by quantifying viral RNA or infectious virus particles. The compound's ability to inhibit WNV NS2B-NS3 protease activity in a cellular context would confirm its cell permeability and antiviral efficacy. However, detailed cell-based assay protocols for SID-852843 are not the primary focus of the available literature.
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| Animal Protocol |
Specific in vivo animal study protocols for SID-852843 are not detailed in standard reference sources. As a research compound for viral protease inhibition, in vivo studies would typically involve animal models of West Nile Virus infection. A common protocol would be to infect mice with WNV and then administer the compound via a suitable route (e.g., intraperitoneal or oral). The efficacy would be assessed by monitoring survival rates, viral load in tissues, and clinical signs of infection. The compound's pharmacokinetic properties and toxicity would also be evaluated in these studies to determine its therapeutic potential.
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| ADME/Pharmacokinetics |
The compound degrades rapidly in pH 8 buffer with a half-life of 1-2 hours. [1]
Specific pharmacokinetic (PK) data for SID-852843 are not extensively reported in the general literature. As a small-molecule inhibitor, its PK properties would be typical of drug-like compounds and would include parameters such as absorption, distribution, metabolism, and excretion. These would be determined in preclinical species to assess its oral bioavailability, half-life, and clearance. The compound's ability to cross the blood-brain barrier might be relevant for treating WNV encephalitis. Detailed PK studies are essential for advancing the compound toward in vivo efficacy and safety studies. |
| Toxicity/Toxicokinetics |
Specific toxicology data for SID-852843 are not typically provided in research summaries, as it is a research tool rather than a clinical candidate. Toxicity studies would be part of a full preclinical development program and would include acute and repeated-dose toxicity studies in animals to identify target organs and establish a safety margin. The compound's selectivity for the WNV protease over human proteases is a key factor in its potential safety profile. As an inhibitor of a viral target, off-target effects on host enzymes would be a primary concern in toxicological evaluation.
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| References | |
| Additional Infomation |
Benzoic acid [5-amino-1-(4-methoxyphenyl)sulfonyl-3-pyrazolyl] ester is a benzoic acid ester.
SID-852843 is a pyrazole benzoic acid ester derivative that was identified as a hit from high-throughput screening (HTS) of a small molecule library through the NIH Molecular Libraries Initiative (MLI). It is an allosteric inhibitor of WNV NS2B-NS3 proteinase. Due to its rapid hydrolysis in aqueous buffer (half-life 1-2 h), it is of limited use as a tool to investigate the biochemistry and enzymatic kinetics of WNV NS2B-NS3 proteinase in vitro. The compound's data were deposited in the PubChem database under AID 577 and AID 653. [1] SID-852843 is a research compound identified as a potent and reversible inhibitor of the West Nile Virus NS2B-NS3 proteinase. It exhibits an IC50 value of 105.0 nM against this target in fluorescence-based assays. The compound is selective for the WNV protease over the Dengue type 2 virus protease, making it a useful probe for studying flaviviral protease biology and for developing specific antiviral therapies. It is used in research on viral infections, particularly for understanding the replication mechanisms of flaviviruses. SID-852843 is not an approved drug but is a valuable tool for antiviral drug discovery. |
| Molecular Formula |
C17H15N3O5S
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|---|---|
| Molecular Weight |
373.38
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| Exact Mass |
373.073
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| Elemental Analysis |
C, 54.69; H, 4.05; N, 11.25; O, 21.42; S, 8.59
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| CAS # |
909859-19-4
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| PubChem CID |
655490
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.592
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
580
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
FQICFDBMQBCJDT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15N3O5S/c1-24-13-7-9-14(10-8-13)26(22,23)20-15(18)11-16(19-20)25-17(21)12-5-3-2-4-6-12/h2-11H,18H2,1H3
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| Chemical Name |
[5-amino-1-(4-methoxyphenyl)sulfonylpyrazol-3-yl] benzoate
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| Synonyms |
909859-19-4; MLS000033898; ML024; SID-852843
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (267.82 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.70 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6782 mL | 13.3912 mL | 26.7824 mL | |
| 5 mM | 0.5356 mL | 2.6782 mL | 5.3565 mL | |
| 10 mM | 0.2678 mL | 1.3391 mL | 2.6782 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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