| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 0.021 μM (GLS1)
GLS1 Inhibitor-1 specifically targets glutaminase 1 (GLS1), the enzyme responsible for the first step in glutaminolysis, which converts glutamine to glutamate. By inhibiting GLS1, the compound blocks the conversion of glutamine to glutamate, depriving cancer cells of a key carbon source for the TCA cycle and a precursor for glutathione synthesis. This leads to metabolic stress, oxidative stress, and ultimately cell death. The inhibition is potent, with an IC50 of 0.021 microM for the purified enzyme. |
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| ln Vitro |
In cell-free biochemical assays, GLS1 Inhibitor-1 demonstrates potent inhibition of GLS1 enzyme activity. Using a glutamate dehydrogenase-coupled assay, the compound is incubated with recombinant GLS1 and glutamine. The production of NADH from NAD+ is monitored spectrophotometrically at 340 nm. The compound exhibits an IC50 of 0.021 microM, indicating high potency. Selectivity over other glutaminases and metabolic enzymes has been demonstrated, confirming its specificity for GLS1.
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| ln Vivo |
In vitro, GLS1 Inhibitor-1 shows potent anti-proliferative activity against cancer cell lines. It inhibits the proliferation of PC-3 prostate cancer cells with an IC50 of 0.3 nM. It also exhibits potent anti-tumor effects against NCI-H1703 lung cancer cells, with a growth inhibition 50% (GI50) value of 0.011 microM. The mechanism of action involves the induction of metabolic stress and oxidative stress, leading to cell cycle arrest and apoptosis in sensitive cancer cell lines.
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| Enzyme Assay |
For a non-cell GLS1 activity assay, recombinant human GLS1 is incubated in an assay buffer (e.g., 50 mM Tris-HCl, pH 8.0) with 10 mM glutamine and varying concentrations of GLS1 Inhibitor-1 (0-10 microM). The reaction is initiated by adding the enzyme and is run for 30-60 minutes at 37degC. The amount of glutamate produced is then measured using a glutamate detection kit, which couples glutamate to colorimetric or fluorometric signal. The IC50 is calculated from the inhibition curve.
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| Cell Assay |
For cell-based proliferation assays, PC-3 cells are seeded in 96-well plates (3,000-5,000 cells/well) in RPMI-1640 medium with 10% FBS and allowed to attach overnight. The next day, the medium is replaced with fresh medium containing GLS1 Inhibitor-1 at concentrations ranging from 0.001 nM to 10 uM. The cells are incubated for 72-96 hours. Cell viability is then measured by adding the CellTiter-Glo reagent to each well, incubating for 10 minutes, and recording luminescence. The IC50 is determined by fitting the dose-response data using non-linear regression analysis.
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| Animal Protocol |
The in vivo efficacy of GLS1 Inhibitor-1 is evaluated in mouse xenograft models of cancer. For example, nude mice bearing subcutaneous NCI-H1703 lung cancer xenografts are administered the compound by oral gavage (e.g., 10-100 mg/kg) twice daily. After several weeks of treatment, tumor volumes are measured regularly with calipers. At the end of the study, tumors are excised and weighed. GLS1 Inhibitor-1 has been shown to exhibit significant anti-tumor activity in such models, with a favorable pharmacokinetic profile and a good safety margin.
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| ADME/Pharmacokinetics |
GLS1 Inhibitor-1 exhibits moderate pharmacokinetic properties. It has been optimized for oral administration, with good bioavailability and plasma exposure. The compound is metabolically stable and is typically formulated in a vehicle such as 0.5% methylcellulose for in vivo studies. For research use, it is stored as a powder at -20degC, where it is stable for up to three years, and in solution at -80degC for up to one year.
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| Toxicity/Toxicokinetics |
Specific toxicity data for GLS1 Inhibitor-1 is not publicly available. However, as a drug candidate that has advanced to Phase 1 clinical trials, it has undergone extensive preclinical toxicology studies to establish safety. Common side effects of GLS1 inhibitors may include gastrointestinal distress and fatigue due to the importance of glutamine metabolism in healthy proliferating tissues. The compound is for research use only and not for human consumption.
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| References | |
| Additional Infomation |
GLS1 Inhibitor-1 (IPN60090) is a research chemical that has progressed to Phase 1 clinical trials (NCT03894540) for the treatment of solid tumors. It represents a novel class of anticancer agents targeting cancer cell metabolism. The compound is particularly potent in cancer cells with KRAS or KEAP1 mutations, which are often dependent on glutamine metabolism for survival. It is a valuable tool for studying the role of glutaminolysis in cancer biology.
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| Molecular Formula |
C19H21N7O2S
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|---|---|
| Molecular Weight |
411.48
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| CAS # |
1832646-52-2
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| Appearance |
White to light yellow solid powder
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| SMILES |
S1C(NC([C@H](C2C=CC=CC=2)OC)=O)=NN=C1N[C@H]1CN(C2=CC=CN=N2)CC1
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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) |
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
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| 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 | 2.4303 mL | 12.1513 mL | 24.3025 mL | |
| 5 mM | 0.4861 mL | 2.4303 mL | 4.8605 mL | |
| 10 mM | 0.2430 mL | 1.2151 mL | 2.4303 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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