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| Targets |
Myeloperoxidase (MPO)
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| ln Vitro |
MPO-IN-3 is a potent inhibitor of myeloperoxidase, as described in patent WO2013068875A1 (example 191). Myeloperoxidase is a heme-containing enzyme belonging to the peroxidase superfamily that catalyzes the formation of hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride ions. MPO inhibition represents a therapeutic strategy for reducing oxidative stress and tissue damage in inflammatory diseases. No specific IC50 value is publicly available for MPO-IN-3, but it is reported to be a "potent" inhibitor. The compound is a 2-thiopyrimidine derivative.
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| ln Vivo |
No specific in vivo data available for MPO-IN-3; however, as a potent MPO inhibitor, it has potential for in vivo efficacy in animal models of cardiovascular disease, acute inflammatory conditions, and chronic inflammatory diseases. Patent WO2013068875A1 describes the synthesis of MPO-IN-3 as part of a series of MPO inhibitors intended for therapeutic use, suggesting that in vivo data may exist in the patent but is not publicly detailed. In vivo studies would involve administration to rodents, measurement of MPO activity in plasma or tissues, and assessment of inflammatory and oxidative stress endpoints.
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| Enzyme Assay |
Recombinant human myeloperoxidase (MPO) or MPO isolated from human neutrophils is used. The enzyme activity assay measures the peroxidase activity of MPO using a chromogenic or fluorogenic substrate. A typical assay uses Amplex Red (10-acetyl-3,7-dihydroxyphenoxazine) as substrate in the presence of hydrogen peroxide (H2O2). The reaction is incubated at room temperature or 37degC for 10-30 minutes in phosphate-buffered saline (PBS, pH 7.4). The product (resorufin) is measured by fluorescence (excitation 530-560 nm, emission 585-590 nm) or absorbance (570 nm). Alternatively, a TMB (tetramethylbenzidine) or ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay can be used. MPO-IN-3 is pre-incubated with the enzyme for 5-10 minutes before substrate addition. IC50 values are determined from dose-response curves. The concentration range tested is typically 0.1 nM-100 uM. The patent example 191 likely describes the synthesis and initial characterization of MPO-IN-3 as an MPO inhibitor. For detailed protocols, refer to the patent WO2013068875A1.
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| Cell Assay |
For cellular MPO inhibition studies, human neutrophils isolated from whole blood or HL-60 cells differentiated into neutrophil-like cells can be used. Cells are cultured in RPMI-1640 with 10% FBS and differentiated with DMSO (1.25%) for 5-7 days. Cells are treated with MPO-IN-3 (0.1-1000 nM) for 1-4 hours, then stimulated with phorbol 12-myristate 13-acetate (PMA, 100 nM) or opsonized zymosan to activate MPO release and activity. MPO activity in the supernatant is measured using the Amplex Red/H2O2 assay as described above. Cell viability is assessed by trypan blue exclusion or MTT assay. Myeloperoxidase protein levels can be quantified by ELISA. Intracellular reactive oxygen species (ROS) production can be measured using DCFH-DA fluorescent probe. The effect of MPO inhibition on neutrophil extracellular trap (NET) formation can also be assessed. No specific cellular data for MPO-IN-3 is publicly available; these are generic protocols for MPO inhibitors.
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| Animal Protocol |
No published in vivo animal study for MPO-IN-3. Based on typical protocols for MPO inhibitors, in vivo efficacy studies can be conducted in rodent models of inflammation. For example, in the zymosan-induced neutrophilic peritonitis model: mice are administered MPO-IN-3 (0.1-10 mg/kg) orally or intraperitoneally. After 1-2 hours, zymosan (0.5-1 mg) is injected intraperitoneally to induce neutrophil recruitment. After 4-6 hours, peritoneal lavage fluid is collected. MPO activity in the lavage fluid is measured using the Amplex Red/H2O2 assay. In a cardiovascular model (e.g., myocardial ischemia-reperfusion injury): mice are subjected to temporary ligation of the left anterior descending coronary artery, followed by reperfusion. MPO-IN-3 is administered before ischemia or at reperfusion. Infarct size is measured by TTC staining, and MPO activity in heart tissue is measured. Inflammatory markers (IL-6, TNF-alpha, MPO) and oxidative stress markers (8-isoprostane, protein carbonylation) are measured in plasma and tissues. These protocols are generic; specific studies for MPO-IN-3 are not publicly available.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data for MPO-IN-3. Based on its molecular properties (MW 371.88, LogP estimated ~2-3 from structure), it is likely to have moderate oral bioavailability. The compound contains a thioamide/thiopyrimidine group, which may be metabolized by flavin-containing monooxygenases (FMOs) or CYP enzymes. Plasma half-life, Cmax, AUC, clearance, volume of distribution, and protein binding have not been publicly reported. Solubility: DMSO 100 mg/mL (268.90 mM). For in vivo studies, a typical formulation for MPO inhibitors is 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline or 10% DMSO + 90% corn oil. Storage: 4degC, stored under nitrogen, away from moisture.
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| Toxicity/Toxicokinetics |
No specific toxicity data for MPO-IN-3. As an MPO inhibitor, the primary expected on-target effect is modulation of oxidative stress and inflammation, which is the intended mechanism. MPO is involved in host defense against pathogens; therefore, MPO inhibition may increase susceptibility to infections, particularly in the context of chronic use. Off-target inhibition of other peroxidases (e.g., thyroid peroxidase, lactoperoxidase) could potentially affect thyroid hormone synthesis or other physiological processes. In the patent WO2013068875A1, MPO-IN-3 was selected as one of the example compounds, suggesting it likely passed initial toxicity screening (e.g., hERG, CYP inhibition, genotoxicity) to be considered a "potent" inhibitor. However, no specific toxicity data are publicly available. For research use only; handle with standard laboratory precautions (gloves, lab coat, eye protection).
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| References | |
| Additional Infomation |
MPO-IN-3 (CAS: 1435469-45-6) is a potent myeloperoxidase (MPO) inhibitor disclosed as example 191 in patent WO2013068875A1 (2-thiopyrimidines). Myeloperoxidase is a heme-containing enzyme that catalyzes the formation of hypochlorous acid (HOCl) and other reactive oxidants, contributing to oxidative stress and tissue damage in inflammatory diseases. MPO-IN-3 is a research tool for studying MPO biology and evaluating the therapeutic potential of MPO inhibition in cardiovascular diseases (e.g., atherosclerosis, heart failure), inflammatory conditions (e.g., COPD, asthma, arthritis), and neurodegenerative diseases. Molecular formula: C16H22ClN3O3S, molecular weight: 371.88. Purity: up to 99.73%. Solubility: DMSO 100 mg/mL (268.90 mM). Storage: 4degC, stored under nitrogen, away from moisture. Not approved for clinical use. Reference: Philip Albert Carpino, et al. 2-thiopyrimidiones. WO2013068875A1. For research use only.
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| Molecular Formula |
C16H22CLN3O3S
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| Molecular Weight |
371.88
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| Exact Mass |
373.122
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| CAS # |
1435469-45-6
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| PubChem CID |
89557813
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
24
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| Complexity |
470
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C1C=C(OC)C=CC=1C1=CC(=O)NC(=S)N1CCCCN)C.Cl
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| InChi Key |
LFHGRTIMOGIDTB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H23N3O3S.ClH/c1-21-11-5-6-12(14(9-11)22-2)13-10-15(20)18-16(23)19(13)8-4-3-7-17;/h5-6,9,13H,3-4,7-8,10,17H2,1-2H3,(H,18,20,23);1H
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| Chemical Name |
1-(4-aminobutyl)-6-(2,4-dimethoxyphenyl)-2-sulfanylidene-1,3-diazinan-4-one;hydrochloride
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 (268.90 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6890 mL | 13.4452 mL | 26.8904 mL | |
| 5 mM | 0.5378 mL | 2.6890 mL | 5.3781 mL | |
| 10 mM | 0.2689 mL | 1.3445 mL | 2.6890 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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