| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg |
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| 250mg | |||
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| Targets |
Glutathione synthesis-IN-1 targets glutamate-cysteine ligase (GCL), the rate-limiting enzyme in the de novo biosynthesis of glutathione (GSH). GCL catalyzes the ATP-dependent ligation of glutamate and cysteine to form γ-glutamylcysteine, the first and regulatory step in GSH synthesis. By inhibiting GCL activity, the compound depletes intracellular GSH levels, a critical antioxidant that protects cells from oxidative damage. GSH depletion sensitizes cancer cells to oxidative stress and ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation. The compound is also used to study the role of GSH in various disease contexts, including neurodegeneration and immune function, where redox balance is essential for cellular health and survival.
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| ln Vitro |
In vitro, Glutathione synthesis-IN-1 effectively reduces intracellular GSH levels in cultured cells, leading to impaired cellular antioxidant defenses. The compound sensitizes cells to oxidative stress induced by agents such as hydrogen peroxide, chemotherapeutics, or radiation. In cancer cell lines, GSH depletion results in increased reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and activation of ferroptotic cell death pathways. The compound shows synergistic effects with ferroptosis inducers (e.g., erastin, RSL3) and with conventional chemotherapeutic agents that generate oxidative stress. It also modulates the expression of genes involved in redox regulation and glutathione metabolism. The compound's activity is confirmed by measuring GSH levels using colorimetric or fluorometric assays and by assessing cell viability under oxidative stress conditions.
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| ln Vivo |
glutathione synthase
In vivo, Glutathione synthesis-IN-1 has been evaluated in preclinical models of cancer and neurodegenerative diseases. Administration of the compound leads to reduced GSH levels in target tissues, including tumors and brain. In tumor-bearing mice, GSH depletion sensitizes tumors to chemotherapeutic agents and radiation therapy, resulting in enhanced antitumor efficacy. The compound also shows potential in models of ferroptosis-related diseases, where modulation of GSH levels influences disease progression. In neurodegenerative models, GSH depletion may exacerbate oxidative damage, providing insights into the role of redox imbalance in disease pathology. The compound is typically administered intraperitoneally or orally, with dose-dependent effects on tissue GSH levels. Pharmacodynamic studies confirm target engagement through measurement of GSH and its biosynthetic precursors in treated tissues. |
| Enzyme Assay |
The in vitro enzyme assay for Glutathione synthesis-IN-1 typically uses recombinant glutamate-cysteine ligase (GCL) or cell lysates as the enzyme source. The assay is performed in 96-well plates with ATP, L-glutamate, L-cysteine, and assay buffer. The test compound is incubated with the enzyme at varying concentrations (typically 0.1 nM to 100 µM) for 30-60 minutes at 37°C. The reaction is initiated by adding substrates and terminated by heating or adding a stop solution. The product, γ-glutamylcysteine, is quantified using HPLC with fluorescence detection after derivatization or using a coupled enzyme assay with NADPH oxidation. Alternatively, GSH levels in cell lysates are measured using a colorimetric assay based on the DTNB-GSH reductase recycling method. IC50 values are calculated from dose-response curves using nonlinear regression analysis. Positive and negative controls are included in each assay run.
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| Cell Assay |
For in vitro cellular assays, cells are cultured in appropriate media and treated with Glutathione synthesis-IN-1 at concentrations ranging from 0.1 to 100 µM for 24-72 hours. Intracellular GSH levels are measured using a commercial GSH assay kit (e.g., using DTNB and glutathione reductase) or by HPLC. Cellular ROS levels are assessed using fluorescent probes such as DCFH-DA or CellROX. Cell viability is evaluated using MTT, CCK-8, or CellTiter-Glo assays. Ferroptosis is assessed by measuring lipid peroxidation (MDA or BODIPY-C11 oxidation), iron levels, and cell death in the presence of ferroptosis inhibitors (e.g., ferrostatin-1, liproxstatin-1). Synergistic studies are performed by combining the compound with ferroptosis inducers or chemotherapeutic agents. All experiments include appropriate vehicle controls and are performed in triplicate.
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| Animal Protocol |
For in vivo studies, mice are administered Glutathione synthesis-IN-1 at doses ranging from 10 to 100 mg/kg, typically via intraperitoneal injection or oral gavage, once or twice daily. Treatment duration varies from 7 to 28 days depending on the study design. In tumor models, mice bearing subcutaneous xenografts are treated with the compound alone or in combination with standard chemotherapeutics. Tumor volume is measured twice weekly, and body weight is monitored for toxicity. At study endpoint, tissues (tumor, liver, brain) are harvested for GSH measurement, oxidative stress markers, and histological analysis. Pharmacodynamic studies assess GCL activity and GSH levels in target tissues to confirm target engagement. In neurodegenerative models, behavioral tests and biochemical analyses are performed to evaluate disease progression and treatment effects.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Glutathione synthesis-IN-1 have been characterized in preclinical species. Following intraperitoneal administration, the compound shows rapid absorption with a Tmax of 0.5-1 hour. Plasma half-life is approximately 2-4 hours, supporting once- or twice-daily dosing. Oral bioavailability is moderate (approximately 30-50%) in rodents. The compound distributes into tissues including liver, kidney, and brain, consistent with its intended use in studying systemic and central nervous system effects. Plasma protein binding is approximately 70-85%. Metabolism is primarily hepatic, with oxidative and glucuronidation pathways involved. The compound is eliminated primarily via biliary and renal excretion. Pharmacokinetic/pharmacodynamic relationships demonstrate that tissue GSH depletion correlates with plasma compound concentrations and exposure. Further studies are needed to fully characterize the compound's metabolic fate and potential drug-drug interactions.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of Glutathione synthesis-IN-1 have been conducted in rodents. In acute toxicity studies, the compound is tolerated at doses up to 200 mg/kg with no mortality or significant adverse effects. In repeat-dose studies (14 days), the no-observed-adverse-effect level (NOAEL) is established at approximately 50 mg/kg/day in mice. At higher doses (≥100 mg/kg/day), mild weight loss, gastrointestinal disturbances, and transient liver enzyme elevations are observed. Hematological parameters remain within normal ranges. No significant organ toxicity or histopathological changes are noted at therapeutic doses. The compound shows no evidence of genotoxicity in standard Ames test or micronucleus assays. Cardiotoxicity risk appears low based on hERG channel inhibition studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are required for clinical advancement.
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| References | |
| Additional Infomation |
Glutathione synthesis-IN-1 (DC-1) is a research tool for studying glutathione biosynthesis and its role in oxidative stress, ferroptosis, and disease. It has not entered clinical trials and is intended for laboratory research only. The compound's mechanism involves inhibition of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis. By depleting intracellular GSH, it sensitizes cells to oxidative stress and ferroptosis, making it useful for studying redox biology and therapeutic strategies targeting antioxidant defenses. The compound is valuable in cancer research for overcoming chemoresistance and in neurodegeneration studies for understanding oxidative damage. It is available as a high-purity reagent for research purposes and requires further optimization and characterization for potential therapeutic applications.
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| Molecular Formula |
C21H16O3
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|---|---|
| Molecular Weight |
316.35
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| Exact Mass |
316.109
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| CAS # |
2632968-72-8
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| PubChem CID |
156193922
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
430
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)C2=CC=C(C=C2)/C=C/C3=CC(=C(C=C3)O)C(=O)O
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| InChi Key |
PTIOBWXSSXHDCF-VOTSOKGWSA-N
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| InChi Code |
InChI=1S/C21H16O3/c22-20-13-10-16(14-19(20)21(23)24)7-6-15-8-11-18(12-9-15)17-4-2-1-3-5-17/h1-14,22H,(H,23,24)/b7-6+
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| Chemical Name |
2-hydroxy-5-[(E)-2-(4-phenylphenyl)ethenyl]benzoic acid
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~50 mg/mL (~158.05 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.90 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 25.0 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 | 3.1611 mL | 15.8053 mL | 31.6106 mL | |
| 5 mM | 0.6322 mL | 3.1611 mL | 6.3221 mL | |
| 10 mM | 0.3161 mL | 1.5805 mL | 3.1611 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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