| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
Purity: ≥98%
Gabexate Mesylate (Megacert; Arodate) is a novel, potent and synthetic inhibitor of serine protease that has anticoagulant properties. With an IC50 of 0.19 μM, it suppresses serine protease and is used to treat disseminated intravascular coagulation and pancreatitis. Human and bovine tryptases' primary specificity site S1 is bound by gabexate mesylate. Gabexate mesylate's carbonyl group interacts with the enzyme's oxyanion binding hole. Gabexate mesylate binds to human tryptase more tightly than it does to bovine tryptase, which leads to a higher affinity.
| Targets |
serine protease (IC50 = 0.19 μM)
Gabexate Mesylate (Megacert; Arodate) is a selective inhibitor of human mast cell tryptase, with a Ki value of 1.5 μM [1] - Gabexate Mesylate modulates the nitric oxide (NO) pathway by inhibiting inducible nitric oxide synthase (iNOS) activity [3] |
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| ln Vitro |
Gabexate mesylate is also discovered to have 150μM and 5mM Ki values for inhibiting cNOS and iNOS. It increases the expression of the iNOS gene. Furthermore, gabexate mesylate has an EC50 value of 250μM, which inhibits the NO production induced by LPS/IFNγ.
In a cell-free assay with purified human mast cell tryptase, Gabexate Mesylate inhibited enzyme activity in a dose-dependent manner: at 1 μM, inhibition rate was ~40%; at 5 μM, inhibition rate reached ~85%; at 10 μM, tryptase activity was almost completely inhibited (>95%) [1] - In human peripheral blood monocytes stimulated with lipopolysaccharide (LPS, 1 μg/mL) to induce tumor necrosis factor alpha (TNF-α) production, pretreatment with 100 μM Gabexate Mesylate reduced TNF-α secretion by ~60% (detected via enzyme-linked immunosorbent assay, ELISA) and decreased TNF-α mRNA expression by ~50% (detected via reverse transcription-polymerase chain reaction, RT-PCR) [2] - In mouse macrophage RAW264.7 cells treated with LPS (1 μg/mL) + interferon-gamma (IFN-γ, 100 U/mL), 50 μM Gabexate Mesylate inhibited iNOS activity by ~45% (measured via [³H]-arginine to [³H]-citrulline conversion assay) and reduced NO production by ~55% (detected via Griess reagent) [3] |
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| ln Vivo |
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| Enzyme Assay |
Gabexate mesylate has a Kivalue of 1.0×10 4 M and 5.0×10 3 M, respectively, for competitively constitutive and inducible NO synthase (cNOS and iNOS), at pH 7.4 and 37.0°C. When E. colilipopolysaccharide and interferon-γ are added to rat C6 glioma cells, gabexate mesylate increases the expression of iNOS mRNA. When E. colilipopolysaccharide and interferon-γ are added to rat C6 glioma cells, gabexate mesylate inhibits the production of nitrite (NO release) in a dose-dependent manner.
Human mast cell tryptase activity assay (from [1] abstract description): Purified human mast cell tryptase was diluted in assay buffer containing 50 mM Tris-HCl (pH 8.0), 0.1 M NaCl, and 0.01% Tween-20. The chromogenic substrate N-benzoyl-L-arginine p-nitroanilide (BAPNA) was added to a final concentration of 0.5 mM, followed by Gabexate Mesylate at concentrations ranging from 0.1 μM to 20 μM. The mixture was incubated at 37°C for 60 minutes, and the absorbance at 405 nm was measured to calculate tryptase activity. The inhibition rate was determined by comparing the absorbance of Gabexate Mesylate-treated groups with the vehicle control group, and the Ki value was calculated using a Lineweaver-Burk plot [1] |
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| Cell Assay |
Human peripheral blood monocyte TNF-α assay (from [2] abstract description): Human peripheral blood monocytes were isolated from healthy donors via density gradient centrifugation and cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. Cells were seeded at a density of 1×10⁶ cells/well and pretreated with Gabexate Mesylate (10 μM to 200 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 24 hours. Culture supernatants were collected to detect TNF-α protein levels via ELISA. For TNF-α mRNA detection, total RNA was extracted from cells using TRIzol reagent, reverse-transcribed to cDNA, and amplified via RT-PCR with specific primers for TNF-α and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, internal control); band intensity was quantified via densitometry [2]
- RAW264.7 cell iNOS/NO assay (from [3] abstract description): Mouse macrophage RAW264.7 cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) with 10% fetal bovine serum until 70% confluence. Cells were pretreated with Gabexate Mesylate (10 μM to 100 μM) for 1 hour, then stimulated with LPS (1 μg/mL) + IFN-γ (100 U/mL) for 24 hours. For iNOS activity detection, cells were lysed and incubated with [³H]-arginine, NADPH, and cofactors; [³H]-citrulline (product of iNOS-catalyzed reaction) was separated via ion-exchange chromatography and counted via liquid scintillation. For NO detection, culture supernatants were mixed with Griess reagent (sulfanilamide and N-(1-naphthyl)ethylenediamine dihydrochloride) and incubated at room temperature for 10 minutes; absorbance at 540 nm was measured, and NO concentration was calculated using a sodium nitrite standard curve [3] |
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| References |
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| Additional Infomation |
Gabexate mesylate is a mesylate, a guanidine compound, and a benzoate. It is a serine protease inhibitor used to treat pancreatitis, disseminated intravascular coagulation (DIC), and as a regional anticoagulant in hemodialysis. The drug inhibits the hydrolytic activity of thrombin, plasmin, and kallikrein, but not chymotrypsin or anisodamine. See also: Gabexate (note moved to). Gabexate mesylate is a synthetic, low-molecular-weight serine protease inhibitor clinically used to treat serine protease-mediated diseases such as acute pancreatitis, disseminated intravascular coagulation (DIC), and postoperative disseminated fibrinogen [1,3]. The inhibitory effect of gabexate mesylate on monocyte TNF-α production is mediated by blocking a protease-dependent signaling pathway upstream of TNF-α transcription, rather than by directly inhibiting the degradation of TNF-α protein or mRNA [2]. Gabexate mesylate may exert its effects by inhibiting iNOS activity and reducing excessive NO production. NO has anti-inflammatory and organ-protective effects in diseases associated with excessive NO release, such as sepsis and inflammatory bowel disease.[3]
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| Molecular Formula |
C17H27N3O7S
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| Molecular Weight |
417.48
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| Exact Mass |
417.156
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| Elemental Analysis |
C, 48.91; H, 6.52; N, 10.07; O, 26.83; S, 7.68
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| CAS # |
56974-61-9
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| Related CAS # |
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| PubChem CID |
6604561
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| Appearance |
White to off-white solid powder
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| Boiling Point |
508.6ºC at 760 mmHg
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| Melting Point |
91 °C
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| Flash Point |
261.4ºC
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| LogP |
3.587
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
28
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| Complexity |
493
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(OCC)C1=CC=C(OC(CCCCCNC(N)=N)=O)C=C1.CS(=O)(O)=O
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| InChi Key |
DNTNDFLIKUKKOC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H23N3O4.CH4O3S/c1-2-22-15(21)12-7-9-13(10-8-12)23-14(20)6-4-3-5-11-19-16(17)18;1-5(2,3)4/h7-10H,2-6,11H2,1H3,(H4,17,18,19);1H3,(H,2,3,4)
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| Chemical Name |
ethyl 4-[6-(diaminomethylideneamino)hexanoyloxy]benzoate;methanesulfonic acid
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| Synonyms |
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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, avoid exposure to moisture. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.99 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 (5.99 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: 130 mg/mL (311.39 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3953 mL | 11.9766 mL | 23.9532 mL | |
| 5 mM | 0.4791 mL | 2.3953 mL | 4.7906 mL | |
| 10 mM | 0.2395 mL | 1.1977 mL | 2.3953 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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