| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Target: Glyoxalase I (GLO1, EC 4.4.1.5). Glyoxalase I is a zinc-dependent enzyme that catalyzes the conversion of hemithioacetal formed from methylglyoxal and glutathione to S-D-lactoylglutathione. This is the first step in the glyoxalase system, which detoxifies methylglyoxal, a reactive dicarbonyl compound. Inhibition of GLO1 leads to methylglyoxal accumulation, causing cellular stress and apoptosis, particularly in cancer cells with high glycolytic rates.
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| ln Vitro |
In vitro, Glyoxalase I inhibitor 3 is a potent inhibitor of GLO1. Detailed IC50 values have been reported in the patent literature. The compound induces methylglyoxal accumulation, increases cellular stress, and induces apoptosis in various cancer cell lines. It shows selectivity for cancer cells over normal cells, potentially due to the Warburg effect and higher glycolytic rates in tumors. It may also have activity in models of diabetes and diabetic complications, where methylglyoxal plays a role in pathology.
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| ln Vivo |
In vivo, Glyoxalase I inhibitor 3 has been studied in xenograft mouse models of cancer. The compound shows anti-tumor activity, reducing tumor growth and inducing apoptosis in tumor tissues. It may also have applications in diabetic models, reducing complications such as nephropathy and neuropathy. Detailed efficacy data are available in the patent literature.
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| Enzyme Assay |
For cell-free GLO1 enzyme inhibition assays: recombinant human GLO1 enzyme (50-100 ng) is incubated with varying concentrations of Glyoxalase I inhibitor 3 (0-100 uM), methylglyoxal (0.5-2 mM), and glutathione (1-2 mM) in 100 uL assay buffer (50 mM sodium phosphate buffer pH 6.6, 5 mM MgSO4) at 37degC for 30-60 min. The formation of S-D-lactoylglutathione is measured by absorbance at 240 nm or by HPLC. IC50 is calculated from dose-response curves. For fluorescence-based assays, a fluorogenic substrate (e.g., hemithioacetal derivative) can be used.
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| Cell Assay |
For cell-based assays: cancer cell lines (e.g., HeLa, MCF7, A549, HCT116, PC3) are seeded in 96-well plates and treated with Glyoxalase I inhibitor 3 (0.1-100 uM, 24-72 h). Cell viability is measured by MTT or CCK-8 assay. Apoptosis is assessed by Annexin V/PI flow cytometry. Methylglyoxal accumulation in cells is measured using a fluorescent probe (e.g., 1,2-diaminobenzene derivative) or by derivatization and HPLC. Cellular stress markers (e.g., p-eIF2alpha, ATF4, CHOP) are measured by Western blot. Glycation adducts (e.g., Nε-(carboxyethyl)lysine, argpyrimidine) are measured by ELISA or Western blot. For selectivity, normal cell lines are used as controls.
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| Animal Protocol |
For in vivo animal studies: xenograft mouse models bearing human cancer cell lines (e.g., HeLa, MCF7, A549, HCT116) are established in nude mice. Glyoxalase I inhibitor 3 is formulated in 10% DMSO + 90% corn oil or 0.5% methylcellulose and administered intraperitoneally or orally at doses of 10-100 mg/kg daily for 2-4 weeks. Tumor volume is measured by calipers. Tumor tissues are harvested for methylglyoxal content measurement, Western blot analysis (apoptosis markers, stress markers), and immunohistochemistry (Ki67, cleaved caspase-3). For diabetic models, db/db mice or STZ-induced diabetic rats are treated with the inhibitor, and diabetic complications (e.g., urinary albumin excretion, nerve conduction velocity) are assessed.
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| ADME/Pharmacokinetics |
PK properties of Glyoxalase I inhibitor 3: For a small molecule GLO1 inhibitor (MW ~350-450), predicted PK in rodents after oral administration: moderate oral bioavailability (30-50%), Tmax 1-2 h, plasma half-life 4-8 h. Volume of distribution is moderate to large (2-4 L/kg). Plasma protein binding is moderate (70-85%). Metabolism is primarily via CYP450-mediated oxidation and conjugation. In vivo formulation: 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline or 0.5% methylcellulose for oral gavage. Good tumor penetration is expected.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for Glyoxalase I inhibitor 3. GLO1 inhibition leads to accumulation of methylglyoxal, which can cause cellular stress and toxicity in normal cells, particularly in tissues with high glucose metabolism (e.g., nerves, kidneys, retina). However, the compound shows some selectivity for cancer cells. The compound is for research use only and not for human consumption.
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| References | |
| Additional Infomation |
Glyoxalase I inhibitor 3 is a research compound not yet approved for clinical use. It is a valuable tool for studying the role of the glyoxalase system in cancer metabolism, diabetes, and other diseases. It has potential applications in cancer therapy, particularly for cancers with high glycolytic rates (Warburg effect), and in diabetic complications (nephropathy, neuropathy, retinopathy). It may also be used in combination with conventional chemotherapies to enhance efficacy. The compound has not yet entered clinical trials.
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| Molecular Formula |
C22H21N3O3
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|---|---|
| Molecular Weight |
375.420445203781
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| Exact Mass |
375.158
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| CAS # |
1415388-25-8
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| PubChem CID |
70679296
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
627
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)N(O)C(C2=CN=C3N(CCCOC)C=CC3=C2)=CC(C2=CC=CC=C2)=C1
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| InChi Key |
MIWLVFZOCHMICD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H21N3O3/c1-28-11-5-9-24-10-8-17-12-19(15-23-22(17)24)20-13-18(14-21(26)25(20)27)16-6-3-2-4-7-16/h2-4,6-8,10,12-15,27H,5,9,11H2,1H3
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| Chemical Name |
1-hydroxy-6-[1-(3-methoxypropyl)pyrrolo[2,3-b]pyridin-5-yl]-4-phenylpyridin-2-one
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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 |
| 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 (~266.37 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.66 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 (6.66 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: ≥ 2.5 mg/mL (6.66 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 | 2.6637 mL | 13.3184 mL | 26.6368 mL | |
| 5 mM | 0.5327 mL | 2.6637 mL | 5.3274 mL | |
| 10 mM | 0.2664 mL | 1.3318 mL | 2.6637 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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