| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
Glutaminase 1 (GLS1) / Glutaminase C (GAC) isozyme. Glutaminase-IN-3 is a potent inhibitor of GLS1 with an IC50 of 0.24 uM. It blocks the conversion of glutamine to glutamate, a critical step for cellular energy production and biosynthesis in highly proliferative cancer cells that rely on glutamine addiction (anaplerosis).
|
|---|---|
| ln Vitro |
Glutaminase-IN-3 potently inhibits GLS1 enzymatic activity in cell-free assays, with an IC50 of 0.24 uM for GAC. In cancer cell lines, it exhibits antiproliferative effects. It inhibits the proliferation of PC3 and LNCaP prostate cancer cells with IC50s of 6.14 uM and 2.13 uM, respectively. It is less toxic to non-cancerous CCD-1072Sk fibroblasts (IC50 = 15.39 uM).
|
| ln Vivo |
In vivo efficacy for Glutaminase-IN-3 has been described in patent literature (WO2014089048A1) showing it has potential antitumor activity. While specific published in vivo data for this exact compound are less abundant, the mechanism of action suggests it could suppress tumor growth in xenograft models by blocking anaplerosis and inducing metabolic stress in GLS1-dependent tumors.
|
| Enzyme Assay |
For non-cellular GLS1 inhibition assays, purified recombinant human GLS1 (GAC isoform) is incubated in a reaction buffer containing glutamine. Glutaminase-IN-3 is added at various concentrations. The amount of glutamate produced is measured using a glutamate dehydrogenase-coupled assay that converts NAD+ to NADH, which is quantified by measuring absorbance at 340 nm. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
For cellular proliferation assays, PC3 or LNCaP prostate cancer cells are seeded in 96-well plates. Cells are treated with increasing concentrations of Glutaminase-IN-3 (0.1-50 uM) for 72 hours. Cell viability is assessed using the MTT or CellTiter-Glo luminescent assay. IC50 values are calculated from the cell viability vs. compound concentration curves. Metabolomic analysis can confirm reduced glutamate and TCA cycle intermediates.
|
| Animal Protocol |
For preclinical animal studies, Glutaminase-IN-3 would likely be formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline for intraperitoneal or oral administration to mice bearing subcutaneous PC3 or LNCaP xenografts. Tumor volume is measured bi-weekly. At the end of the study, tumors are harvested to measure glutaminase activity, glutamine consumption, and glutamate/ATP levels. however, specific published protocols are limited.
|
| ADME/Pharmacokinetics |
Glutaminase-IN-3 has a molecular formula of C19H19F3N6O2S and a molecular weight of 452.45 g/mol. It is soluble in DMSO (≥10 mg/mL) and is provided as a solid. For in vitro use, stock solutions (e.g., 10 mM) are prepared in DMSO and stored at -20degC, protected from light. It is stable for at least one year under recommended storage conditions.
|
| Toxicity/Toxicokinetics |
According to safety datasheets from commercial suppliers, Glutaminase-IN-3 is not for human or veterinary use. It is for laboratory research purposes only. Acute toxicity data is limited, but standard precautions should be taken: avoid inhalation, skin contact, and ingestion. It should be handled in a well-ventilated area with appropriate personal protective equipment (lab coat, gloves).
|
| References | |
| Additional Infomation |
Glutaminase-IN-3 is covered under patent WO2014089048A1 (compound 657). It is one of several potent GLS1 inhibitors being developed to exploit the metabolic vulnerabilities of cancer cells, often in combination with other inhibitors of oxidative phosphorylation or glycolysis. It is not an FDA-approved drug.
|
| Molecular Formula |
C19H19F3N6O2S
|
|---|---|
| Molecular Weight |
452.45
|
| Exact Mass |
452.124
|
| CAS # |
1439399-45-7
|
| PubChem CID |
74982828
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Index of Refraction |
1.619
|
| LogP |
2.38
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
31
|
| Complexity |
573
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=CC(=C1)OC(F)(F)F)CC(=O)NC2=NN=C(C=C2)CCCCC3=NN=C(S3)N
|
| InChi Key |
SXFQBUKKIKMRPM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H19F3N6O2S/c20-19(21,22)30-14-6-3-4-12(10-14)11-16(29)24-15-9-8-13(25-26-15)5-1-2-7-17-27-28-18(23)31-17/h3-4,6,8-10H,1-2,5,7,11H2,(H2,23,28)(H,24,26,29)
|
| Chemical Name |
N-[6-[4-(5-amino-1,3,4-thiadiazol-2-yl)butyl]pyridazin-3-yl]-2-[3-(trifluoromethoxy)phenyl]acetamide
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO: 50 mg/mL (110.51 mM)
|
|---|---|
| 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 | 2.2102 mL | 11.0509 mL | 22.1019 mL | |
| 5 mM | 0.4420 mL | 2.2102 mL | 4.4204 mL | |
| 10 mM | 0.2210 mL | 1.1051 mL | 2.2102 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
