| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
Target: 4-MMPB targets 15-lipoxygenase (15-LOX) with an IC50 of 0.5 μM against soybean 15-LOX [1]
- Target: 4-MMPB specifically inhibits 15-LOX, with an IC50 of 0.7 μM against human recombinant 15-LOX-1, and no significant inhibitory activity against 5-LOX and 12-LOX (IC50 > 50 μM) [2] |
|---|---|
| ln Vitro |
For DPPH bleaching, 4-MMPB's IC50 is 69.6 μM[2]. 4-MMPB has cytotoxic effects on the human PC-3 and HFF3 cell lines [4]. PC-3 cells are exposed to 4-MMPB (41.48 µM) for 72 hours, which causes DNA damage and apoptosis [4].
15-LOX Enzymatic Inhibitory Activity: 4-MMPB exhibits potent and selective inhibition of 15-LOX. In in vitro enzyme reaction systems, 0.5 μM concentration inhibits 50% of soybean 15-LOX activity, and the inhibition rate reaches 92% at 10 μM [1] - Inhibition Mechanism: 4-MMPB binds to the active site of 15-LOX in a competitive manner, competing with the substrate linoleic acid for the binding pocket, with a Ki value of 0.3 μM. Molecular docking shows that the compound binds to key amino acid residues of the enzyme through hydrogen bonds and hydrophobic interactions, stabilizing the enzyme-inhibitor complex [2] - Intracellular 15-LOX Inhibitory Effect: In tumor cells expressing 15-LOX, treatment with 4-MMPB (1 μM) for 24 hours reduces the production of 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a catalytic product of 15-LOX, by 78%, confirming its retention of enzymatic inhibitory activity intracellularly [2] |
| Enzyme Assay |
15-LOX Activity Inhibition Assay (Soybean Source): Linoleic acid was used as the substrate. A reaction buffer (pH 7.4) containing 15-LOX was prepared, and serial concentrations of 4-MMPB (0.01-10 μM) were added for pre-incubation for 10 minutes, followed by the addition of the substrate to initiate the reaction. After incubation at 37℃ for 30 minutes, the characteristic absorption peak (234 nm) of the reaction product was detected by spectrophotometry to calculate the enzyme activity inhibition rate, and the IC50 value was fitted by nonlinear regression analysis [1]
- Human Recombinant 15-LOX-1 Inhibition Assay: A human 15-LOX-1 recombinant expression system was constructed to purify the recombinant enzyme. 4-MMPB (0.05-20 μM), recombinant enzyme, and linoleic acid substrate were added to the reaction system. After incubation at 37℃ for 20 minutes, 15(S)-HETE was separated and quantified by high-performance liquid chromatography to analyze the inhibitory effect of the compound at different concentrations; parallel experiments with 5-LOX and 12-LOX were set up to verify selectivity [2] - Inhibition Kinetics Analysis Assay: The concentration of 15-LOX was fixed, and different substrate (linoleic acid) concentrations (10-100 μM) and 4-MMPB concentrations (0, 0.2, 0.5, 1 μM) were set for enzymatic reactions. The Lineweaver-Burk curve was analyzed by double reciprocal plotting to determine the inhibition type as competitive inhibition, and the Ki value was calculated [2] |
| Cell Assay |
Cell Viability Assay[4]
Cell Types: DU145 cells, PC-3 cells, HFF3 cells Tested Concentrations: 9.57 µM, 19.94 µM, 39.88 µM, 79.77 µM, 159.53 µM Incubation Duration: 24 hrs (hours), 48 hrs (hours), 72 hrs (hours) Experimental Results: Cell inhibition Viability (PC-3 cells, IC50=79.76 µM; 24 hrs (hours), 51.05 µM; 48 hrs (hours), 41.48 µM; 72 hrs (hours), IC50=255.25 µM; 24 hrs (hours), 130.81 µM; 48 hrs (hours), 98.91 µM; HFF3 cells 72 hrs (hours)). Intracellular 15(S)-HETE Detection Assay: Tumor cells expressing 15-LOX were seeded in 6-well plates and cultured to 70% confluency. Serial concentrations of 4-MMPB (0.1-10 μM) were added, and culture was continued for 24 hours. Cell culture supernatants were collected, lipid metabolites were extracted by solid-phase extraction, and the content of 15(S)-HETE was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to evaluate the intracellular 15-LOX inhibitory effect [2] |
| References |
|
| Additional Infomation |
Structural characteristics: 4-MMPB is a pyrimido[4,5-b][1,4]benzothiazine derivative whose chemical structure contains a pyrimidine ring and a benzothiazine ring. The 4-methoxymethyl (-CH2OCH3) group is a key substituent that maintains its 15-lipoxygenase (15-LOX) inhibitory activity [1]. Research and development background: 4-MMPB is a small molecule inhibitor designed and synthesized for 15-LOX. 15-LOX is involved in the metabolism of polyunsaturated fatty acids, and its abnormal activation is associated with diseases such as inflammation and tumors. This compound is expected to be a potential drug for treating related diseases [1]
- Selectivity: 4-MMPB has subtype-selective inhibition of 15-LOX, acting only on 15-LOX (including plant-derived and human 15-LOX-1), and has no significant inhibitory effect on other lipoxygenase subtypes (5-LOX, 12-LOX) or cyclooxygenases (COX-1, COX-2), thereby reducing the risk of off-target side effects [2] |
| Molecular Formula |
C₁₆H₁₉N₅S
|
|---|---|
| Molecular Weight |
313.42
|
| Exact Mass |
313.136
|
| CAS # |
928853-86-5
|
| PubChem CID |
44423602
|
| Appearance |
Light yellow to orange solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
532.1±60.0 °C at 760 mmHg
|
| Flash Point |
275.6±32.9 °C
|
| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
| Index of Refraction |
1.649
|
| LogP |
3.35
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
22
|
| Complexity |
387
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
HYPHGMNLWIKEMB-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H19N5S/c1-11-14-15(22-13-6-4-3-5-12(13)18-14)19-16(17-11)21-9-7-20(2)8-10-21/h3-6,18H,7-10H2,1-2H3
|
| Chemical Name |
4-methyl-2-(4-methylpiperazin-1-yl)-5H-pyrimido[4,5-b][1,4]benzothiazine
|
| Synonyms |
15-lipoxygenaseinhibitor4;MMPB4; MMPB4
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~7.69 mg/mL (~24.54 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.77 mg/mL (2.46 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 7.7 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: ≥ 0.77 mg/mL (2.46 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 7.7 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: ≥ 0.77 mg/mL (2.46 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 | 3.1906 mL | 15.9530 mL | 31.9061 mL | |
| 5 mM | 0.6381 mL | 3.1906 mL | 6.3812 mL | |
| 10 mM | 0.3191 mL | 1.5953 mL | 3.1906 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
