| Size | Price | Stock | Qty |
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| 500mg |
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Purity: ≥98%
| Targets |
Irsogladine targets multiple pathways to exert its mucosal protective effects. It is a non-selective inhibitor of phosphodiesterase isozymes, increasing intracellular cyclic AMP content. It is also a PDE4 inhibitor and binds to muscarinic acetylcholine receptors. Irsogladine enhances gap junction intercellular communication through M1 muscarinic acetylcholine receptor binding and via upregulation of connexins 32 and 26.
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| ln Vitro |
Irsogladine up-regulates GJIC between PC cells via regulation of the PKA pathway. It also suggests a useful adjuvant of Irsogladine to pancreatic cancer therapy. Irsogladine produces the increase of intracellular cAMP content via non-selective inhibition of PDE isozymes, which may be a key mechanism involved in its gastroprotective actions
Preliminary in vitro studies revealed that Irsogladine maleate (IM) blocks growth factor-induced endothelial cell expression of plasminogen activator (PA) and inhibits migration in a variety of endothelial cell types [1] IM diminishes PA activity in vitro [1] In vitro, Irsogladine is a PDE4 inhibitor and muscarinic acetylcholine receptor binder. It enhances gap junction intercellular communication via upregulation of connexins 32 and 26. It exhibits gastric cytoprotection partly mediated by endogenous nitric oxide. These in vitro studies confirm its multi-target mechanism of action. |
| ln Vivo |
Irsogladine treatment (300 and 500 mg/kg/day) resulted in a dose-dependent reduction of angiogenesis in wild-type mice by 21 and 45.3% (P < 0.02, P < 0.001), in tPA-deficient mice by 42.6 and 46% (P < 0.001, P < 0.001), and in uPA-deficient mice by 27.2 and 46% (P < 0.05, p < 0.001), respectively. Irsogladine inhibits bFGF-induced angiogenesis in wild-type, tPA-knockout, and uPA-knockout mice.
In wild-type C57Bl/6 mice, oral administration of Irsogladine maleate at 300 and 500 mg/kg/day resulted in a dose-dependent reduction of bFGF-induced corneal neovascularization by 21% (P<0.02) and 45.3% (P<0.001), respectively, compared to vehicle control [1] In tPA-deficient (tPA-/-) mice, IM at 300 and 500 mg/kg/day reduced angiogenesis by 42.6% (P<0.001) and 46% (P<0.001), respectively [1] In uPA-deficient (uPA-/-) mice, IM at 300 and 500 mg/kg/day reduced angiogenesis by 27.2% (P<0.05) and 46% (P<0.001), respectively [1] No quantitative differences in neovascularization were observed between transgenic mouse strains within each treatment group [1] In vivo, Irsogladine is used for the treatment of peptic ulcer disease and acute gastritis. It is also used to improve gastric mucosal lesions in acute and chronic gastritis. Treatment with Irsogladine results in a dose-dependent reduction of angiogenesis. It is an orally active compound. |
| Enzyme Assay |
Non-cellular enzyme assays for Irsogladine involve measuring its inhibition of PDE activity using purified PDE enzymes and appropriate substrates. Its binding to muscarinic acetylcholine receptors can be assessed using receptor binding assays. These assays confirm the compound's multi-target pharmacology.
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| Cell Assay |
In vitro cell-based assays for Irsogladine are conducted using gastric epithelial cells to assess its cytoprotective effects. Cells are treated with the compound, and markers of cell viability, inflammation, and gap junction communication are measured. These experiments are crucial for confirming its mechanism of action.
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| Animal Protocol |
300 and 500 mg/kg Mice
For the mouse cornea micropocket assay: Mice (6-8 weeks old, C57Bl/6 wild-type, tPA-/-, uPA-/-) were acclimated and caged in groups of five or less. IM was suspended in 0.5% carboxymethylcellulose and administered via oral gavage once daily for 3 days prior to pellet implantation and for 6 consecutive days after implantation at doses of 300 mg/kg or 500 mg/kg (0.2 ml volume). Vehicle control received 0.5% carboxymethylcellulose alone. On day 0, mice were anesthetized with inhalational methoxyflurane. A corneal pocket was surgically created in each eye with a Von Graefe cataract knife. A freshly made pellet (0.34 × 0.34 × 0.2 mm) composed of sucrose aluminum sulfate and hydron polymer containing 100 ng bFGF was implanted into each pocket, positioned 1.0-1.2 mm from the circumferential limbic artery. Erythromycin ophthalmic ointment was applied to each operated eye. On postoperative day 6, mice were anesthetized and corneas were photographed using a slit-lamp biomicroscope with 40× magnification by a blinded observer. Maximal vessel length and clock hours of contiguous neovascularization were measured with a calibrated reticule. Angiogenesis was quantified by calculating vascular area using a modified half-ellipse formula: Area (mm²) = vessel length (mm) × clock hours × π × 0.2 mm. All experiments were repeated at least three times [1] In vivo animal studies for Irsogladine are conducted in animal models of peptic ulcer disease and gastritis to evaluate its mucosal protective efficacy. The compound is administered orally, and gastric mucosal lesions, inflammation, and angiogenesis are assessed. These studies are essential for validating its in vivo efficacy. |
| ADME/Pharmacokinetics |
Irsogladine is an orally active compound with a molecular weight of 256.09 g/mol. It is soluble in DMSO at 2 mg/mL but has limited solubility in water and ethanol. Detailed pharmacokinetic parameters such as half-life and bioavailability are not extensively documented in standard summaries but would be evaluated in clinical studies.
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| Toxicity/Toxicokinetics |
No signs of significant drug toxicity (weight loss, decreased activity, decreased consumption of food or water, abnormal behavior) were noted in any groups of animals treated with Irsogladine maleate up to 500 mg/kg/day [1]
Irsogladine has an established safety profile from its clinical use in Japan. Common side effects are generally mild and may include gastrointestinal disturbances. Comprehensive toxicological data are available from its clinical use. Irsogladine is an approved drug in Japan for the treatment of peptic ulcer disease and gastritis. |
| References |
J Surg Res.1998 Jul 1;77(2):126-31;Pancreas.2002 Nov;25(4):373-7.
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| Additional Infomation |
6-(2,5-Dichlorophenyl)-1,3,5-triazine-2,4-diamine is a dichlorobenzene. Isogradin is being investigated in the clinical trial NCT02581696 (Drug interactions and safety of lafutidine and isogradin maleate in healthy adult volunteers).
Irsogladine maleate is an antiulcer drug (gap-junction modulator) used in Japan for the treatment of peptic ulcer disease. It has been suggested to stabilize diabetic retinopathy, a condition resulting from excessive vascularization of the retina. The mechanism of action of IM may be independent of plasminogen activation, as it significantly diminishes angiogenesis in both PA-deficient (tPA-/- and uPA-/-) and wild-type mice. Enhanced PA activity occurs during angiogenesis and correlates with tumor aggressiveness; inhibition of PA/plasmin system and/or angiogenesis may represent a novel approach to malignancy treatment [1] Irsogladine is a mucosal protective drug developed in Japan for the treatment of peptic ulcer disease and acute gastritis. It increases intracellular cAMP via PDE inhibition and exhibits gastric cytoprotection mediated by nitric oxide. Irsogladine is an approved drug in Japan for peptic ulcer disease and gastritis. |
| Molecular Formula |
C9H7CL2N5
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| Molecular Weight |
256.09
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| Exact Mass |
255.007
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| CAS # |
57381-26-7
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| Related CAS # |
Irsogladine maleate;84504-69-8
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| PubChem CID |
3752
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| Appearance |
White to off-white solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
552.2±60.0 °C at 760 mmHg
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| Melting Point |
268-269°C
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| Flash Point |
287.8±32.9 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.706
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| LogP |
2.08
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
16
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| Complexity |
232
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ATCGGEJZONJOCL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H7Cl2N5/c10-4-1-2-6(11)5(3-4)7-14-8(12)16-9(13)15-7/h1-3H,(H4,12,13,14,15,16)
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| Chemical Name |
6-(2,5-dichlorophenyl)-1,3,5-triazine-2,4-diamine
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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 |
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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: 3 mg/mL (11.71 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 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: ≥ 3 mg/mL (11.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9049 mL | 19.5244 mL | 39.0488 mL | |
| 5 mM | 0.7810 mL | 3.9049 mL | 7.8098 mL | |
| 10 mM | 0.3905 mL | 1.9524 mL | 3.9049 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02581696 | Completed | Drug: Lafutidine Drug: Irsogladine maleate |
Peptic Ulcer | Boryung Pharmaceutical Co., Ltd | August 2015 | Phase 1 |
| NCT02759224 | Completed | Drug: Lafutidine Drug: Irsogladine maleate |
Gastric Ulcer | Boryung Pharmaceutical Co., Ltd | April 15, 2016 | Phase 1 |
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