| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
NBTGR targets nucleoside transporters, specifically the equilibrative nucleoside transporters (ENTs) that mediate the cellular uptake of nucleosides. The compound is a potent inhibitor of nucleoside transport by human erythrocytes, where initial rates of uridine uptake are reduced to zero upon exposure of cells to 1 microM NBTGR. NBTGR inhibits adenosine uptake with a Ki of 70 nM, demonstrating its high potency and affinity for the nucleoside transporter. The compound's mechanism of action involves binding to the nucleoside transporter and blocking the translocation of nucleosides across the cell membrane. The primary target of NBTGR is the equilibrative nucleoside transporter 1 (ENT1, also known as SLC29A1), which is the main transporter for adenosine and other nucleosides in many cell types. By inhibiting ENT1, NBTGR increases extracellular adenosine concentrations, which can activate adenosine receptors and modulate various signaling pathways.
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| ln Vitro |
group of purine ribonucleosides with an alkylarylthiol substituent at the purine 6-position are strong inhibitors of several phases of nucleoside metabolism involving ribosyl transfer. NBTGR is one of the chemicals that inhibits nucleoside transport in human erythrocytes; when cells are exposed to 1 μM NBTGR, the initial rate of uridine uptake reduces to zero. The inhibitor was tightly bound since repeated washing did not restore the uridine transport ability of NBTGR-treated cells. NBTGR suppresses the inflow of uridine, inosine, and cytidine without reducing the absorption of the respective bases or D-glucose or L-leucine. Uridine antagonizes the inhibition of uridine transport by NBTGR in a concentration-dependent manner. NBTGR and similar chemicals appear to interact with systems that increase nucleoside transport [2].
NBTGR demonstrates potent in vitro activity as a nucleoside transport inhibitor. The compound inhibits adenosine uptake with a Ki of 70 nM. In human erythrocytes, exposure to 1 microM NBTGR reduces the initial rates of uridine uptake to zero, demonstrating the compound's complete inhibition of nucleoside transport. NBTGR is one of the most potent inhibitors of nucleoside transport described. The compound's activity has been characterized in multiple cell types and transport systems. Its inhibition of nucleoside transport is competitive and reversible. NBTGR's high potency and specificity for nucleoside transporters make it a valuable tool for studying nucleoside metabolism and signaling. The compound's effects on adenosine uptake have been particularly well-characterized. |
| ln Vivo |
In vivo, NBTGR is used to study the physiological roles of nucleoside transporters and adenosine signaling. By inhibiting nucleoside transport, the compound increases extracellular adenosine concentrations, which can activate adenosine receptors and modulate various physiological processes. NBTGR has been used in studies of neurotransmission, cardiovascular function, and immune regulation. The compound's ability to inhibit adenosine uptake in vivo has been demonstrated in various animal models. Comprehensive in vivo efficacy studies using NBTGR as a therapeutic agent have not been reported, as the compound is primarily a research tool rather than a drug candidate. The compound's effects are mediated through the inhibition of nucleoside transporters and subsequent modulation of extracellular nucleoside concentrations.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for NBTGR are not standard, as the compound is a nucleoside transport inhibitor rather than an enzyme inhibitor or receptor ligand. However, nucleoside transport assays can be performed to measure the compound's inhibitory activity. Cells (typically erythrocytes or cultured cell lines) are incubated with radiolabeled nucleosides (e.g., [3H]-adenosine or [3H]-uridine) in the presence or absence of varying concentrations of NBTGR. The uptake of the radiolabeled nucleoside is measured by filtering cells and counting radioactivity. IC50 or Ki values are calculated from dose-response curves using non-linear regression analysis. The assay is performed in appropriate buffer systems with controls for non-specific uptake and binding. NBTGR's inhibition of nucleoside transport is complete at 1 microM in human erythrocytes. Each concentration is typically tested in duplicate or triplicate.
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| Cell Assay |
In vitro cellular assays for NBTGR are performed using cells expressing nucleoside transporters, typically erythrocytes or cultured cell lines. Cells are incubated with radiolabeled nucleosides (e.g., [3H]-adenosine or [3H]-uridine) in the presence or absence of varying concentrations of NBTGR. The uptake of the radiolabeled nucleoside is measured, and the concentration-dependent inhibition is determined. Alternatively, the effects of NBTGR on downstream signaling pathways can be assessed. For example, adenosine receptor-mediated signaling can be measured by cAMP accumulation or ERK phosphorylation following treatment with NBTGR and exogenous adenosine. Cell viability is assessed in parallel using standard assays to ensure that observed effects are not due to cytotoxicity. The compound's effects on nucleoside transport are typically quantified as percent inhibition of uptake at various concentrations.
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| Animal Protocol |
In vivo animal studies for NBTGR are conducted to study the physiological roles of nucleoside transporters and adenosine signaling. Rodents are typically used, and NBTGR is administered via injection (intraperitoneal, intravenous, or subcutaneous). In studies of neurotransmission, NBTGR may be administered to modulate adenosine levels in the brain. In cardiovascular studies, the compound's effects on heart rate, blood pressure, and coronary blood flow may be assessed. In immune studies, the compound's effects on lymphocyte function and inflammation may be evaluated. Pharmacokinetic studies assess drug concentrations in plasma and target tissues. Animals are monitored for clinical signs and body weight. The compound's in vivo effects are mediated through inhibition of nucleoside transport and subsequent modulation of extracellular nucleoside concentrations.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NBTGR have been characterized in preclinical studies. The compound has a molecular formula of C17H18N6O6S and a molecular weight of 434.43 g/mol. Its chemical name is (2R,3R,4S,5R)-2-(2-amino-6-{[(4-nitrophenyl)methyl]sulfanyl}-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol. NBTGR is soluble in DMSO and other organic solvents. The compound is typically administered by injection due to its polarity and limited oral bioavailability. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and bioavailability have been characterized in animal models. The compound's ability to cross the blood-brain barrier has been studied. Its pharmacokinetic profile supports its use as a research tool.
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| Toxicity/Toxicokinetics |
NBTGR is intended for laboratory research use only and has not undergone comprehensive toxicology testing. As a nucleoside transport inhibitor, the compound would be expected to have effects on adenosine signaling and various physiological processes. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside transport studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. The compound's effects on cardiovascular function and neurotransmission would be of particular interest in toxicology assessments. Comprehensive toxicological characterization including genotoxicity, cardiotoxicity, and repeated-dose toxicity studies has not been reported in the public domain. The compound is not approved for human use and is strictly intended for research purposes.
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| References |
[1]. Turnheim K, et al. Inhibition of adenosine uptake in human erythrocytes by adenosine-5'-carboxamides, xylosyladenine, dipyridamole, hexobendine, and p-nitrobenzylthioguanosine. Biochem Pharmacol. 1978;27(18):2191-7.
[2]. Parterson A, et al. Nucleoside Transport II Inhibition by p-Nitrobeazylthiogoanosine and Related Compounds. Can. J. Biochem. 49,271-274 (1971) |
| Additional Infomation |
NBTGR (p-Nitrobenzylthioguanosine) is a potent inhibitor of nucleoside transport with a Ki of 70 nM for adenosine uptake. It is a purine ribonucleoside analog that inhibits the uptake of nucleosides by equilibrative nucleoside transporters, particularly ENT1. NBTGR reduces the initial rates of uridine uptake to zero at 1 microM in human erythrocytes. The compound has a molecular formula of C17H18N6O6S and a molecular weight of 434.43 g/mol. NBTGR is widely used in scientific research to study nucleoside metabolism and signaling. The compound has not entered clinical trials and has not received regulatory approval for any indication. It is available from research chemical suppliers for non-clinical research purposes only. NBTGR is a valuable research tool for studying the physiological roles of nucleoside transporters and adenosine signaling.
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| Molecular Formula |
C17H18N6O6S
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| Molecular Weight |
434.42600
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| Exact Mass |
434.101
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| CAS # |
13153-27-0
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| PubChem CID |
96048
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.87g/cm3
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| Boiling Point |
858.3ºC at 760mmHg
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| Melting Point |
203-205ºC
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| Flash Point |
472.9ºC
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| Vapour Pressure |
2.2E-31mmHg at 25°C
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| Index of Refraction |
1.844
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| LogP |
1.324
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
608
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1=CC(=CC=C1CSC2=NC(=NC3=C2N=CN3[C@H]4[C@@H]([C@@H]([C@H](O4)CO)O)O)N)[N+](=O)[O-]
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| InChi Key |
BRSNNJIJEZWSBU-XNIJJKJLSA-N
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| InChi Code |
InChI=1S/C17H18N6O6S/c18-17-20-14-11(19-7-22(14)16-13(26)12(25)10(5-24)29-16)15(21-17)30-6-8-1-3-9(4-2-8)23(27)28/h1-4,7,10,12-13,16,24-26H,5-6H2,(H2,18,20,21)/t10-,12-,13-,16-/m1/s1
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| Chemical Name |
(2R,3R,4S,5R)-2-[2-amino-6-[(4-nitrophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
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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 (~230.19 mM)
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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 | 2.3019 mL | 11.5093 mL | 23.0187 mL | |
| 5 mM | 0.4604 mL | 2.3019 mL | 4.6037 mL | |
| 10 mM | 0.2302 mL | 1.1509 mL | 2.3019 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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