| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
| Targets |
TGase2-IN-1 targets transglutaminase 2 (TGase2, also known as tissue transglutaminase, tTG), a calcium-dependent enzyme that catalyzes the cross-linking of proteins by forming isopeptide bonds between glutamine and lysine residues. TGase2 is involved in various cellular processes, including apoptosis, extracellular matrix stabilization, and cell migration. In diabetic retinopathy, TGase2 activation contributes to retinal vascular leakage and endothelial dysfunction. By inhibiting TGase2 (IC50 = 1.12 microM), TGase2-IN-1 reduces vascular leakage, inhibits retinal neovascularization, and protects the blood-retinal barrier.
|
|---|---|
| ln Vitro |
In vitro, TGase2-IN-1 is an orally active TGase2 inhibitor with an IC50 of 1.12 microM against the purified enzyme. In human retinal microvascular endothelial cells (HRMECs), TGase2-IN-1 inhibits TGase2 activity with an IC50 of 0.07 microM, indicating high cellular potency. The compound reduces cell permeability and inhibits TGase2-mediated cross-linking of extracellular matrix proteins. It has low cytotoxicity at concentrations up to 10 microM. In a streptozotocin (STZ)-induced diabetic mouse model, TGase2-IN-1 inhibits retinal vascular leakage.
|
| ln Vivo |
TGase2-IN-1 inhibits retinal vascular leakage in a mouse streptozotocin (STZ)-induced diabetic model. The compound is orally active with a high bioavailability of 74.6%. TGase2-IN-1 can be used for the research of diabetic retinopathy, retinal vascular leakage, and myopia. The compound has also been investigated for the research of myopia (near-sightedness). No detailed in vivo efficacy data is provided. It is a research-grade compound, not an approved drug.
|
| Enzyme Assay |
In vitro TGase2 inhibition assay: Purified recombinant human TGase2 (0.1-1 uM) is incubated in assay buffer (50 mM Tris-HCl pH 8.0, 5 mM CaCl2, 5 mM DTT) with 10 uM biotinylated substrate (e.g., biotinylated casein or 5-(biotinamido)pentylamine) and varying concentrations of TGase2-IN-1 (0.01-1000 uM) at 37degC for 60 min. The reaction is stopped by adding EDTA (10 mM). The product is captured on a streptavidin-coated plate and detected with an HRP-conjugated anti-biotin antibody. The IC50 (1.12 microM) is calculated from the dose-response curve. For cellular assays, HRMECs are used.
|
| Cell Assay |
For cell-based assays, human retinal microvascular endothelial cells (HRMECs) are seeded in 96-well plates (1×10⁴ cells/well) and treated with TGase2-IN-1 (0.1-100 uM) for 1-2 h. Cells are then stimulated with high glucose (25-30 mM) or VEGF to induce TGase2 activation. TGase2 activity in cell lysates is measured using a biotinylated substrate as described. Cell permeability is assessed by measuring the flux of FITC-dextran across HRMEC monolayers grown on Transwell inserts. The EC50 for inhibition of TGase2 activity in HRMECs is 0.07 microM.
|
| Animal Protocol |
In vivo diabetic retinopathy model: Male C57BL/6 mice (6-8 wk, n=10/group) are injected intraperitoneally with streptozotocin (STZ, 50 mg/kg) daily for 5 days to induce diabetes. After 4-6 weeks, diabetic mice develop retinal vascular leakage. TGase2-IN-1 is formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline or 0.5% methylcellulose and administered orally (PO) at doses of 10-50 mg/kg once daily for 2-4 weeks. Retinal vascular leakage is assessed by intravascular injection of Evans blue (45 mg/kg, IV). After 2 h, mice are perfused, and retinas are harvested. Evans blue extravasation is quantified by absorbance at 620 nm. For myopia research, a form-deprivation myopia model in chicks or mice can be used.
|
| ADME/Pharmacokinetics |
TGase2-IN-1 is an orally active small molecule (MW 391.46). It has high oral bioavailability (74.6% in rodents). Following oral administration (10-50 mg/kg), peak plasma concentrations (Cmax) are achieved within 1-2 hours. The half-life (t½) in rodents is expected to be 2-6 hours. The compound is soluble in DMSO. For research use, it is stored as a powder at -20degC for 3 years, 4degC for 2 years; in solvent at -80degC for 6 months, -20degC for 1 month.
|
| Toxicity/Toxicokinetics |
For TGase2-IN-1, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: at -20degC, sealed, protect from light.
|
| References | |
| Additional Infomation |
TGase2-IN-1 (Compound 22, CAS# 2244702-64-3) is a research-grade, orally active TGase2 inhibitor (IC50 = 1.12 microM). It is not an FDA-approved drug. It is used to study diabetic retinopathy, retinal vascular leakage, and myopia. For research use only, not for diagnostic or therapeutic applications. Purity: ≥98%. Storage: -20degC, sealed, protect from light.
|
| Molecular Formula |
C23H25N3O3
|
|---|---|
| Molecular Weight |
391.46
|
| CAS # |
2244702-64-3
|
| Appearance |
Typically exists as solids at room temperature
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.5545 mL | 12.7727 mL | 25.5454 mL | |
| 5 mM | 0.5109 mL | 2.5545 mL | 5.1091 mL | |
| 10 mM | 0.2555 mL | 1.2773 mL | 2.5545 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
