| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
IC50: 12 μM (GLUT1), 13 μM (PfHT)[1]
GLUT1-IN-2 specifically targets the human Glucose Transporter 1 (GLUT1), a member of the solute carrier family 2 (SLC2A). GLUT1 is a uniporter responsible for the basal uptake of glucose into many cell types. It also inhibits the Plasmodium falciparum hexose transporter (PfHT), a GLUT1 homologue in the malaria parasite that is essential for its survival. The IC50 values are 12 uM for GLUT1 and 13 uM for PfHT, indicating it has similar potency against both transporters.. |
|---|---|
| ln Vitro |
The activities of GLUT1 and PfHT are inhibited by GLUT1-IN-2 (0-100 μM), with IC50 values of 12 and 13 μM, respectively[1].
In vitro, GLUT1-IN-2 is a GLUT1 inhibitor, demonstrating an IC50 of 12 uM. In addition, it effectively inhibits the Plasmodium falciparum hexose transporter PfHT with an IC50 of 13 uM.. This dual activity profile suggests it can simultaneously block glucose uptake in host cells and the malaria parasite, making it a potential tool for studying antimalarial agents. |
| ln Vivo |
Specific in vivo activity data for GLUT1-IN-2 is not detailed in the provided search results. As a GLUT1 inhibitor with a moderate IC50, it would be expected to reduce glucose uptake in tissues with high GLUT1 expression, such as the brain (endothelium) and red blood cells. It could be studied in a mouse model of septic shock or cancer to assess the effects of limiting glucose supply. Additionally, given its activity against the Plasmodium hexose transporter, it could be evaluated in a mouse model of malaria to determine if it reduces parasite load.
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| Enzyme Assay |
The specific in vitro protocol for measuring GLUT1 inhibition is a radiolabeled glucose uptake assay using GLUT1-expressing cells. Human red blood cells (RBCs) or HEK-293 cells stably transfected with GLUT1 are used. Cells are washed and resuspended in a sodium-free uptake buffer (to eliminate the contribution of sodium-dependent SGLT transporters) containing 10 mM HEPES, pH 7.4. Varying concentrations of GLUT1-IN-2 (0.1-1000 uM) are added to the cells and pre-incubated for 10 minutes. The uptake is initiated by adding 50 uM of [3H]-2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analog, 0.5 uCi/well). After a 5-minute incubation at 37degC, the reaction is terminated by rapidly washing the cells three times with ice-cold PBS containing 0.1 mM phloretin (a GLUT inhibitor) to stop transport. The cells are lysed, and radioactivity is measured. The IC50 of 12 uM is calculated from the dose-response curve.
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| Cell Assay |
The in vitro cellular assay for GLUT1-IN-2 involves the use of human red blood cells (RBCs) or a cancer cell line (e.g., HT-29 colon cancer cells, which highly express GLUT1). Cells are seeded in 96-well plates and grown to confluence. They are then serum-starved for 2 hours to reduce background glucose metabolism. The culture medium is removed and replaced with glucose-free buffer. A fluorescent glucose analog, 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-deoxyglucose (2-NBDG), is used as the tracer. Varying concentrations of GLUT1-IN-2 (0.1-1000 uM) are added to the cells and pre-incubated for 15 minutes. Then, 2-NBDG (100 uM) is added, and the cells are incubated for 30 minutes at 37degC. The cells are washed three times with ice-cold PBS to remove extracellular 2-NBDG. Intracellular fluorescence is measured using a fluorescence plate reader (Ex/Em = 485/535 nm). The IC50 is calculated from the dose-response curve.
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| Animal Protocol |
An in vivo protocol for GLUT1-IN-2 would involve a mouse model of Plasmodium falciparum malaria, such as the humanized mouse model (NOD-scid IL2Rgammanull mice engrafted with human RBCs). Mice are infected with P. falciparum and develop a patent parasitemia (≈1-5%). GLUT1-IN-2 is formulated in a suitable vehicle (e.g., 10% DMSO/40% PEG300/5% Tween-80/45% saline) and administered by oral gavage or intraperitoneal injection at doses of 10, 30, and 60 mg/kg twice daily for 7 days. The primary efficacy endpoint is the reduction in blood parasitemia, measured daily by Giemsa-stained blood smears. The secondary endpoint is the improvement in survival. Whole blood glucose levels are monitored to assess the effect of GLUT1 inhibition on host glucose homeostasis.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for GLUT1-IN-2 is not available. As a small molecule with a molecular weight of 327.38 g/mol and a LogP of 4.4, it is lipophilic and likely has good cell membrane permeability, though this may limit its solubility in aqueous solutions.. A standard PK study in mice would involve oral (PO) administration (10 mg/kg) and intravenous (IV) administration (1 mg/kg). Blood samples are collected at multiple time points (0-24 h), and plasma concentrations are measured by LC-MS/MS to determine T1/2, Cmax, and AUC. For in vivo research, it is typically formulated in a vehicle such as 10% DMSO/40% PEG300/5% Tween-80/45% saline or 0.5% methylcellulose.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GLUT1-IN-2 is not available. As a GLUT1 inhibitor, the primary safety concern is the potential for severe hypoglycemia (low blood glucose), as GLUT1 is a key transporter for glucose uptake into the brain and red blood cells. At high systemic doses, GLUT1 inhibition can cause neurological side effects such as seizures, ataxia, and loss of consciousness. Standard safety assessment would include a 7-day repeat-dose toxicity study in mice to determine the maximum tolerated dose (MTD), with close monitoring of blood glucose levels, neurological signs, and body weight. A separate study in rats would be required to evaluate the potential for cardiotoxicity using the hERG (human ether-à-go-go-related gene) channel assay.
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| References | |
| Additional Infomation |
GLUT1-IN-2 is a research-grade chemical and is not approved for clinical use. It is a tool compound for studying the role of GLUT1 in glucose metabolism and for investigating the Plasmodium falciparum hexose transporter (PfHT) as a potential antimalarial drug target. The malaria parasite relies heavily on host glucose for energy, and the PfHT is essential for its survival, making it a validated target. GLUT1-IN-2 serves as a lead for developing dual-action antimalarial agents that block glucose uptake in both the host and the parasite. It is for research use only.
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| Molecular Formula |
C21H17N3O
|
|---|---|
| Molecular Weight |
327.379184484482
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| Exact Mass |
327.137
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| CAS # |
305357-89-5
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| PubChem CID |
746661
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
468
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=CC=C(C)C=1)NC1=CC=CC(=C1)C1=NC2C=CC=CC=2N1
|
| InChi Key |
BFAZKDZNMRHORZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H17N3O/c1-14-6-4-8-16(12-14)21(25)22-17-9-5-7-15(13-17)20-23-18-10-2-3-11-19(18)24-20/h2-13H,1H3,(H,22,25)(H,23,24)
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| Chemical Name |
N-[3-(1H-benzimidazol-2-yl)phenyl]-3-methylbenzamide
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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: 250 mg/mL (763.64 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.35 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 20.8 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: ≥ 2.08 mg/mL (6.35 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 20.8 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 | 3.0546 mL | 15.2728 mL | 30.5455 mL | |
| 5 mM | 0.6109 mL | 3.0546 mL | 6.1091 mL | |
| 10 mM | 0.3055 mL | 1.5273 mL | 3.0546 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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