| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
SARS-CoV 3C-like protease (3CLpro) - non-covalent inhibitor (IC50 = 1.5 μM).
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|---|---|
| ln Vitro |
In cell culture, ML188 (0-30 μM; 48 hours) effectively inhibits SARS-CoV replication[1].
The SARS-CoV 3CLpro inhibitor Probe ML188 has a non-covalent mode of action, moderate molecular weight, and proven antiviral activity. The antiviral EC50 value of ML188 in both SARS-CoV-infected and mock-infected cells ranges from 12.9 to 13.4 μM[1]. In vitro enzymatic assays demonstrate that ML188 is a potent, non-covalent inhibitor of the SARS-CoV 3C-like protease (3CLpro) with an IC50 of 1.5 μM. The compound has a non-covalent mode of action, moderate molecular weight, and proven antiviral activity. In cell-based assays, ML188 effectively inhibits SARS-CoV replication in cell culture with antiviral EC50 values ranging from 12.9 to 13.4 μM in infected cells. The compound's ability to inhibit 3CLpro, a key enzyme in the coronavirus life cycle responsible for processing the viral polyprotein, makes it a valuable tool for studying coronavirus replication and for developing antiviral therapeutics. |
| ln Vivo |
In vivo studies on ML188 are limited, as the compound is primarily used as a research tool for in vitro investigations of coronavirus replication and 3CLpro inhibition. The compound has been identified as a valuable tool for studying the modulation of innate immune signaling and the treatment of diseases associated with excessive inflammation, including autoimmune disorders and viral infections. Further studies are needed to assess the compound's pharmacokinetic properties, oral bioavailability, and efficacy in animal models of SARS-CoV infection. The compound's non-covalent mechanism of action and moderate molecular weight make it a promising lead for further optimization.
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| Enzyme Assay |
3CLpro enzymatic activity assays are performed using purified recombinant SARS-CoV 3CLpro enzyme and a fluorogenic peptide substrate that mimics the viral polyprotein cleavage site. The enzyme is incubated with the substrate and varying concentrations of ML188, and the increase in fluorescence due to substrate cleavage is measured over time. The initial reaction rates are calculated, and IC50 values are determined from dose-response curves by non-linear regression analysis. The mechanism of inhibition (competitive, non-competitive, or mixed) is determined by analyzing the effect of substrate concentration on inhibition.
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| Cell Assay |
Cell Line: Vero E6 cells (mock-infected or infected with SARS-CoV)
Concentration: 3, 4, 5, 8,10, 15, 20, 30 μM Incubation Time: 48 hour Result: Against mock-infected and SARS-CoV infected cells. Cellular assays for ML188 typically involve infecting permissive cell lines (such as Vero E6 cells) with SARS-CoV and treating with ML188 at various concentrations. Viral replication is assessed by measuring viral RNA levels by quantitative RT-PCR, viral titers by plaque assay, or viral protein expression by immunofluorescence or Western blotting. The antiviral EC50 is calculated from dose-response curves. Cytotoxicity against mammalian cells is assessed in parallel using MTT or CellTiter-Glo assays to determine the selectivity index. The compound's ability to inhibit viral replication without significant cytotoxicity is essential for its utility as an antiviral research tool. |
| Animal Protocol |
In vivo efficacy of ML188 is evaluated in mouse models of SARS-CoV infection. Mice are infected with the virus and then treated with ML188 via oral or intraperitoneal administration. Viral load in the lungs and other tissues is measured by quantitative RT-PCR or plaque assay. Disease severity is assessed by monitoring body weight loss, clinical signs, and survival. Histopathological examination of lung tissues is performed to assess inflammation and tissue damage. Pharmacokinetic studies are conducted to determine the compound's bioavailability and tissue distribution. The compound's efficacy in vivo is important for validating 3CLpro as a therapeutic target for coronavirus infections.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of ML188 have been characterized to support its use as a research tool. The compound's molecular weight of 433.54 and chemical properties influence its absorption, distribution, metabolism, and excretion (ADME) characteristics. Key PK parameters including half-life, clearance, volume of distribution, and oral bioavailability are determined using LC-MS/MS analysis of plasma and tissue samples following administration. The compound's ability to reach target tissues such as the lungs is important for its efficacy in in vivo studies. The compound's non-covalent mechanism of action and moderate molecular weight are favorable for drug development.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of ML188 is typically conducted in parallel with efficacy studies in cell-based and animal models. Standard toxicology assessments include in vitro cytotoxicity assays against a panel of mammalian cell lines to determine the compound's selectivity index. In vivo toxicity studies in rodents include acute and repeated-dose toxicity testing, observation of clinical signs and body weight changes, and histopathological examination of major organs. As a 3CLpro inhibitor, potential effects on host proteases and off-target effects are carefully monitored. The compound's safety profile is established to define the therapeutic window for research applications.
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| References | |
| Additional Infomation |
N-[(1R)-2-(tert-butylamino)-2-oxo-1-(3-pyridyl)ethyl]-N-(4-tert-butylphenyl)-2-furan carboxamide is a furan compound and also an aromatic amide.
ML188 is a research tool compound used for studying SARS-CoV replication and 3CLpro inhibition, as well as for investigating the modulation of innate immune signaling. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves non-covalent inhibition of the SARS-CoV 3C-like protease (3CLpro), which blocks the processing of the viral polyprotein and inhibits viral replication. This compound is valuable for validating 3CLpro as a therapeutic target for coronavirus infections and for studying the biology of coronavirus replication. ML188 has also been studied for its potential in treating diseases associated with excessive inflammation. |
| Molecular Formula |
C26H31N3O3
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|---|---|
| Molecular Weight |
433.5426
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| Exact Mass |
433.236
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| Elemental Analysis |
C, 72.03 H, 7.21 N, 9.69 O, 11.07
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| CAS # |
1417700-13-0
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| Related CAS # |
1417699-67-2 (racemic);1417700-12-9 (S-isomer);1417700-13-0 (R-isomer);
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| PubChem CID |
46897844
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| Appearance |
White to off-white solid powder
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| LogP |
5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
644
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C([C@@]([H])(C1=C([H])N=C([H])C([H])=C1[H])N(C(C1=C([H])C([H])=C([H])O1)=O)C1C([H])=C([H])C(=C([H])C=1[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H]
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| InChi Key |
JXGIYKRRPGCLFV-JOCHJYFZSA-N
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| InChi Code |
InChI=1S/C26H31N3O3/c1-25(2,3)19-11-13-20(14-12-19)29(24(31)21-10-8-16-32-21)22(18-9-7-15-27-17-18)23(30)28-26(4,5)6/h7-17,22H,1-6H3,(H,28,30)/t22-/m1/s1
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| Chemical Name |
N-[(1R)-2-(tert-Butylamino)-2-oxo-1-pyridin-3-ylethyl]-N-(4-tert-butylphenyl)furan-2-carboxamide
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| Synonyms |
ML188; ML-188; ML 188;
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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 : ~250 mg/mL (~576.65 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (14.42 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 62.5 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: ≥ 6.25 mg/mL (14.42 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 62.5 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: ≥ 6.25 mg/mL (14.42 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 | 2.3066 mL | 11.5330 mL | 23.0659 mL | |
| 5 mM | 0.4613 mL | 2.3066 mL | 4.6132 mL | |
| 10 mM | 0.2307 mL | 1.1533 mL | 2.3066 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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