| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 29.97 μM (EBOV), 47.72 μM (MARV)[1]
SP-187 functions as an α-glucosidase inhibitor. By inhibiting α-glucosidase, an enzyme involved in the processing of glycoproteins in the endoplasmic reticulum, it disrupts the folding and function of viral glycoproteins. This host-targeted approach prevents the proper assembly and release of enveloped viruses, such as filoviruses (e.g., Ebola), influenza, and dengue virus. |
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| ln Vitro |
Using a yield-plaque assay technique, the antiviral activity of iminosugar SP187 (UV-4) against EBOV and MARV is evaluated in vitro, and the IC50 is found. With an IC50 of 29.97 and 47.72 μM for EBOV and MARV, respectively, antiviral activity for SP187 is noted[1].
In vitro, SP-187 has activity against filovirus infections (e.g., Ebola, Marburg). It is also active against influenza and dengue viruses in vitro. Its antiviral activity is characterized by the inhibition of viral replication in cell culture, with EC50 values in the low micromolar range, as measured by plaque reduction or viral RNA quantification. |
| ln Vivo |
Using a mouse model of EBOV infection, the effectiveness of UV-5, the most potent iminosugar studied in vitro, and SP187 (UV-4), the active free base component of UV-4B, is first evaluated. In this work, oral gavage or IP injection of 10 or 100 mg/kg of SP187 or UV-5 is given to C57Bl/6 mice. Dosing began approximately one hour before to infection with 1000 pfu of mouse-adapted EBOV. For ten days, BID dosing was repeated at roughly 12-hour intervals for UV-5 or TID dosing at roughly 8-hour intervals for SP187. The chosen dosages and timing are derived on studies on mouse naïve tolerance. When comparing the iminosugar-treated mice to the vehicle control, no effectiveness is seen[1].
In vivo, SP-187 has been shown to be effective against influenza and dengue viruses in animal models. It has also demonstrated activity against filovirus infections in vivo. It is used for therapeutic purposes against these viral infections in research settings, improving survival and reducing viral load in infected animals. |
| Enzyme Assay |
In vitro enzyme assays for SP-187 typically measure the inhibition of α-glucosidase activity. The enzyme (e.g., from rat intestine or recombinant) is incubated with a suitable substrate (e.g., p-nitrophenyl-α-D-glucopyranoside) in the presence of varying concentrations of the compound. The inhibition of substrate hydrolysis is measured by absorbance, and the IC50 is determined.
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| Cell Assay |
To test the activity of the iminosugars UV-1, UV-2, UV-3, SP187 (UV-4) and UV-5 against EBOV (Zaire-Kikwit) or MARV (Ci67), a yield-plaque assay is conducted in Vero cells. Multiple concentrations of compounds are incubated on 24-well plates of Vero cells for 1h at 8 concentrations (2 fold dilutions starting at 62.5 μM). After ~1h, pretreatment medium is aspirated and virus inoculums added (MOI of 0.1 with EBOV or MARV). After an additional hour of infection, virus inoculum is removed (no washing) and 1 mL of compound medium is added at the final concentration. After incubation for 72 hours, supernatants are harvested and competent viral particles released from the cells are enumerated by plaque assay in duplicate. Percent inhibition is determined by comparing DMSO-treated cells (average value) infected with virus to those treated with compound at the various concentrations. The IC50 are calculated using GraphPad Prism based on the % inhibition at each concentration[1]. |
| Animal Protocol |
Mice[1] Mouseadapted EBOV and MARV-Ravn are used to infect female C57Bl/6 or BALB/c mice with target challenge dose of 1000 pfu via intraperitoneal injection. SP187 (free base) and UV-5 are prepared in acidified water for oral gavage (PO) or in phosphate buffered saline (PBS) for intraperitoneal infection (IP) and subcutaneous (SQ) delivery. SP187 (UV-4) or UV-5 are administered via PO, IP or SQ for 7-10 days starting 30-60 minutes before virus challenge at 5, 10, 20, or 100 mg/kg or vehicle only (water for PO or PBS for IP delivery). Compounds are administered either twice (BID) or three times (TID) daily at 12 or 8 hour intervals, respectively. Weights, morbidity and mortality are monitored for up to 21 days. Animals which displaye severe illness are euthanized based on predefined scoring systems. |
| ADME/Pharmacokinetics |
SP-187 has a molecular formula of C16H33NO5 and a molecular weight of 319.44 g/mol. Its chemical name is (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(9-methoxynonyl)piperidine-3,4,5-triol. It is also known as N-9-DNJ, MON-DNJ, and UV-4B. It is an α-glucosidase inhibitor and is typically stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
SP-187 is an α-glucosidase inhibitor with a well-characterized mechanism of action as a host-targeted antiviral agent. As with any experimental compound, potential toxicity should be evaluated in preclinical studies. It is for research use only and is not approved for human therapeutic use. Common adverse effects may include gastrointestinal disturbances.
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| References | |
| Additional Infomation |
SP-187, also known as N-9-DNJ or UV-4B, is an α-glucosidase inhibitor and host-targeted iminosugar with antiviral activity against filoviruses, influenza, and dengue. The compound is for research use only and is not approved for human therapeutic use.
|
| Molecular Formula |
C16H33NO5
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|---|---|
| Molecular Weight |
319.442
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| Exact Mass |
319.236
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| CAS # |
615253-61-7
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| Related CAS # |
1333144-07-2 (HCl);615253-61-7;
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| PubChem CID |
503982
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| Appearance |
White to off-white solid powder
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| LogP |
0.06
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
22
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| Complexity |
279
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| Defined Atom Stereocenter Count |
4
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| SMILES |
COCCCCCCCCCN1C[C@@H]([C@H]([C@@H]([C@H]1CO)O)O)O
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| InChi Key |
TYTARGBBJQKLAJ-QKPAOTATSA-N
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| InChi Code |
InChI=1S/C16H33NO5/c1-22-10-8-6-4-2-3-5-7-9-17-11-14(19)16(21)15(20)13(17)12-18/h13-16,18-21H,2-12H2,1H3/t13-,14+,15-,16-/m1/s1
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| Chemical Name |
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-(9-methoxynonyl)piperidine-3,4,5-triol
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| Synonyms |
SP 187 MON-DNJ UV-4 SP187 MON DNJ UV4 SP-187
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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 (~313.05 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1305 mL | 15.6524 mL | 31.3048 mL | |
| 5 mM | 0.6261 mL | 3.1305 mL | 6.2610 mL | |
| 10 mM | 0.3130 mL | 1.5652 mL | 3.1305 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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