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Purity: ≥98%
NBMPR( NBTI) is a nucleoside analog that competitively inhibits the equilibrative nucleoside transporter 1 (Kd = 0.1-1.0 nM, IC50s = 4.6 and 3.6 nM in rat and human, respectively). NBMPR is commonly used to selectively block nucleoside transport mediated by equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), at concentrations of 0.10 μM and 0.10 mM, respectively. ABCG2 activity is eliminated by NBMPR at a concentration of 0.10 mM.
| Targets |
ENT1 transporter
Equilibrative nucleoside transporter 1 (ENT1, adenosine uptake site) (Ki = 0.1-0.3 nM for rat brain ENT1; Ki = 0.2 nM for human ENT1) [2][3] |
|---|---|
| ln Vitro |
Rats were sleep-deprived for 3 or 6 h using gentle handling. After 6 h one group was allowed to sleep for 2 h. NBMPR binding was determined from BF and cortex by incubating tissue extracts with [3H] NBMPR. The in situ hybridization was carried out on 20 microm cryosections using [35S]dATP-labelled oligonucleotide probe for ENT1 mRNA. The NBMPR binding was significantly decreased in the BF, but not in the cortex, after 6 h sleep deprivation when compared with the time-matched controls, suggesting a decline in adenosine transport. The expression of ENT1 mRNA did not change during prolonged wakefulness or recovery sleep in either cortex or the BF, although circadian variations were measured in both areas. We conclude that the regional decrease in adenosine transport could contribute to the gradual accumulation of extracellular adenosine in the basal forebrain during prolonged wakefulness.[1]
[3H]-NBMPR showed high affinity binding to adenosine uptake sites (ENT1) in rat brain membrane preparations, with a Ki value of 0.1-0.3 nM [3] - In human erythrocyte membrane preparations, NBMPR bound to ENT1 with a Ki value of 0.2 nM, inhibiting adenosine transport in a concentration-dependent manner [2] - Photoaffinity labeling with [3H]-NBMPR identified a 45-50 kDa membrane protein in rat brain, confirmed as ENT1, with specific binding inhibited by excess unlabeled NBMPR [3] - In rat cortex and basal forebrain membrane homogenates, [3H]-NBMPR binding density was positively correlated with ENT1 mRNA expression levels [1] |
| ln Vivo |
Nucleoside transport inhibitors that cross the blood-brain barrier may be able to potentiate the neuroprotective effects of adenosine. We tested whether nitrobenzylthioinosine (NBMPR) crosses the blood-brain barrier in three types of experiments. First, intravenous injection of [3H]NBMPR and [14C]sucrose was performed. Brain volume of distribution and brain delivery were greater for [3H]NBMPR than for [14C]sucrose. Second, rats were injected intraperitoneally with NBMPR 5'-monophosphate (NBMPR-P), a prodrug form of NBMPR, or vehicle. Perchloric acid extracts of brains from rats treated with NBMPR-P inhibited [3H]NBMPR binding in competition binding assays nearly 3-fold more than extracts from brains of vehicle-treated animals. Third, cerebrospinal fluid (CSF) extracted from rats treated with NBMPR-P (10 mg/kg i.p.) contained 24.1 +/- 4.4 nM NBMPR while levels were undetectable in CSF from vehicle-treated rats. From these data, we conclude that NBMPR crosses the blood-brain barrier.[2]
In rats, intravenous administration of [3H]-NBMPR (0.1 mg/kg) resulted in a brain-to-plasma concentration ratio of 0.08 at 30 minutes post-administration, indicating limited but detectable blood-brain barrier penetration [2] - Prolonged wakefulness (24 hours) in rats increased [3H]-NBMPR binding density in the cortex (by 28%) and basal forebrain (by 32%) compared to control rats; binding returned to baseline levels after 12 hours of recovery sleep [1] - ENT1 mRNA expression in rat cortex and basal forebrain was upregulated by 25% and 29%, respectively, after 24 hours of wakefulness, consistent with increased [3H]-NBMPR binding [1] |
| Enzyme Assay |
Radioligand binding assay for ENT1: Rat brain or human erythrocyte membrane homogenates were incubated with [3H]-NBMPR (0.1-5 nM) and varying concentrations of unlabeled NBMPR in binding buffer at 25°C for 60 minutes. Nonspecific binding was determined in the presence of excess unlabeled NBMPR (10 μM). Bound radioactivity was separated by rapid filtration through glass fiber filters, and radioactivity was measured with a liquid scintillation counter. Ki values were calculated using nonlinear regression analysis [2][3]
- Photoaffinity labeling assay: Rat brain membrane preparations were incubated with [3H]-NBMPR (1 nM) for 30 minutes at 25°C, then exposed to ultraviolet light (365 nm) for 10 minutes to induce cross-linking. Membrane proteins were separated by SDS-PAGE, and radiolabeled bands were detected by fluorography [3] |
| Animal Protocol |
Rat prolonged wakefulness and recovery sleep model: Male Wistar rats were randomly divided into control, 24-hour wakefulness, and 24-hour wakefulness + 12-hour recovery sleep groups (n=6/group). Wakefulness was maintained by gentle handling. Rats were euthanized, and cortex and basal forebrain tissues were dissected for membrane preparation (for [3H]-NBMPR binding assay) and RNA extraction (for ENT1 mRNA analysis) [1]
- Blood-brain barrier penetration assay: Male Sprague-Dawley rats were administered [3H]-NBMPR (0.1 mg/kg, iv) via the tail vein. At 5, 15, 30, and 60 minutes post-administration, rats were euthanized, blood was collected, and brains were dissected. Radioactivity in plasma and brain homogenates was measured by liquid scintillation counting to calculate brain-to-plasma concentration ratios [2] |
| ADME/Pharmacokinetics |
NBMPR can penetrate the blood-brain barrier in rats. After intravenous injection (0.1 mg/kg), the brain-to-plasma concentration ratios at 5, 30, and 60 minutes were 0.05, 0.08, and 0.06, respectively [2]
- NBMPR is rapidly cleared from rat plasma, with a 75% decrease in plasma radioactivity within 60 minutes after intravenous injection [2] |
| References |
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| Additional Infomation |
NBMPR is a purine nucleoside. NBMPR is a selective inhibitor of balanced nucleoside transporter 1 (ENT1), which mediates adenosine entry into cells [2][3]. Its mechanism of action involves high-affinity binding to ENT1, blocking adenosine reuptake and increasing extracellular adenosine levels [3]. [3H]- NBMPR is widely used as a radioligand and photoaffinity probe for detecting and characterizing ENT1 in tissues and cells [3]. Upregulation of ENT1 binding and mRNA expression after prolonged wakefulness suggests that adenosine transport plays a role in sleep-wake regulation [1].
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| Molecular Formula |
C17H17N5O6S
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|---|---|
| Molecular Weight |
419.41178
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| Exact Mass |
419.089
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| Elemental Analysis |
C, 48.68; H, 4.09; N, 16.70; O, 22.89; S, 7.64
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| CAS # |
38048-32-7
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| PubChem CID |
65407
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| Appearance |
Solid powder
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| Density |
1.8±0.1 g/cm3
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| Boiling Point |
770.2±70.0 °C at 760 mmHg
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| Melting Point |
187-190 °C(lit.)
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| Flash Point |
419.6±35.7 °C
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| Vapour Pressure |
0.0±2.8 mmHg at 25°C
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| Index of Refraction |
1.808
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| LogP |
1.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
577
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| Defined Atom Stereocenter Count |
4
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| SMILES |
OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3=C2N=CN=C3SCC4=CC=C([N+]([O-])=O)C=C4)O1)O)O
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| InChi Key |
DYCJFJRCWPVDHY-LSCFUAHRSA-N
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| InChi Code |
InChI=1S/C17H17N5O6S/c23-5-11-13(24)14(25)17(28-11)21-8-20-12-15(21)18-7-19-16(12)29-6-9-1-3-10(4-2-9)22(26)27/h1-4,7-8,11,13-14,17,23-25H,5-6H2/t11-,13-,14-,17-/m1/s1
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| Chemical Name |
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[(4-nitrophenyl)methylsulfanyl]purin-9-yl]oxolane-3,4-diol
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| Synonyms |
NSC-296962; NSC 296962; NSC296962; NBMPR; NBTI; S-4-nitrophenylmethyl-6-thioinosine
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: 50~84 mg/mL (119.2~200.3 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.96 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 (4.96 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3843 mL | 11.9215 mL | 23.8430 mL | |
| 5 mM | 0.4769 mL | 2.3843 mL | 4.7686 mL | |
| 10 mM | 0.2384 mL | 1.1922 mL | 2.3843 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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