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| Targets |
ML359 primarily targets protein disulfide isomerase (PDI), an enzyme responsible for catalyzing the formation and rearrangement of disulfide bonds during protein folding. By inhibiting PDI activity, ML359 disrupts thrombus formation and has been widely used to explore the role of cardiolipin remodeling in disease progression.
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| ln Vitro |
In high-resolution cell lines (HeLa, HEK293, and HepG2), ML359 shows minimal cytotoxicity, and in vitro, it is moderately efficacious in reducing dye aggregation (25% inhibition at 30 μM) [1].
In vitro studies have demonstrated that ML359 is a specific inhibitor of PDI with an IC50 of 250 nM. It shows no cytotoxicity in three human cell lines (HeLa, HEK293, and HepG2) and exhibits some activity in inhibiting platelet aggregation in vitro, with 25% inhibition observed at 30 µM. These findings support its utility in understanding PDI mechanisms in platelet function. |
| ln Vivo |
A laser damage model shows that ML359 reduces thrombosis [2].
In vivo, ML359 has been shown to effectively inhibit thrombosis. By blocking ALCAT1 activity (a downstream effect of PDI inhibition), ML359 helps preserve mitochondrial integrity and improves cellular energy homeostasis. These in vivo effects position ML359 as a potential lead for developing new classes of anti-thrombotic compounds. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for ML359 typically involves measuring PDI activity using a model substrate such as insulin in the presence of dithiothreitol (DTT). The reduction of insulin turbidity is monitored spectrophotometrically at 650 nm. ML359 is pre-incubated with PDI for a set time, and the IC50 is determined by plotting the percentage of remaining activity against compound concentration. The reported IC50 of ML359 against PDI is 250 nM.
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| Cell Assay |
Cellular activity of ML359 is assessed in human cell lines including HeLa, HEK293, and HepG2 to evaluate cytotoxicity, typically using an MTT or CCK-8 assay after 24-72 hours of treatment. Platelet aggregation inhibition is measured in vitro using platelet-rich plasma (PRP) isolated from human blood. Aggregation is induced by agonists such as collagen or ADP, and the extent of aggregation is monitored using a turbidometric aggregometer. ML359 is added at various concentrations (e.g., 30 µM) to determine its inhibitory effect.
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| Animal Protocol |
In vivo efficacy of ML359 is evaluated in animal models of thrombosis, such as the ferric chloride-induced carotid artery injury model in mice or rats. In this model, thrombosis is induced by topical application of FeCl₃, and blood flow is monitored using a Doppler flow probe. ML359 is administered via intravenous injection or oral gavage prior to injury. The time to occlusion and thrombus weight are measured to assess the anti-thrombotic effect.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of ML359 have not been extensively reported in the public domain. As a small molecule with a molecular weight of 417.93 g/mol and a logP consistent with its structure (C23H28ClNO4), it is expected to have moderate oral bioavailability and reasonable tissue distribution. Further studies are needed to fully characterize its ADME profile.
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| Toxicity/Toxicokinetics |
Published data indicate that ML359 shows no cytotoxicity in three human cell lines (HeLa, HEK293, and HepG2), suggesting a favorable safety profile at concentrations up to 30 µM. However, comprehensive toxicology studies, including genotoxicity, cardiotoxicity (hERG), and long-term safety assessments, have not been fully disclosed.
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| References |
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| Additional Infomation |
ML359 is a chemical probe developed for research purposes and has not yet entered clinical trials or received regulatory approval for therapeutic use. Its mechanism of action involves selective and reversible inhibition of PDI, which plays a crucial role in thrombus formation. ML359 is expected to contribute to the development of novel anti-thrombotic agents.
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| Molecular Formula |
C19H18N4O3
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|---|---|
| Molecular Weight |
350.371223926544
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| Exact Mass |
350.1379
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| CAS # |
1069858-99-6
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| Appearance |
Yellow to brown solid powder
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| SMILES |
O1C=CC=C1C(N(CC)C1C2=CC3C=CC(=CC=3N=C2N(C)N=1)OC)=O
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| Synonyms |
ML 359; ML-359; ML359
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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 (~239.27 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.98 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 (5.98 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 (5.98 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 | 2.8541 mL | 14.2706 mL | 28.5413 mL | |
| 5 mM | 0.5708 mL | 2.8541 mL | 5.7083 mL | |
| 10 mM | 0.2854 mL | 1.4271 mL | 2.8541 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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