| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Nucleoside transporter (apparent \(K_i\) for inhibition of uridine influx in human erythrocytes: 33 μM; apparent \(K_i\) for inhibition of high-affinity nitrobenzylthioinosine binding to human erythrocyte membranes: 0.18 mM) [1]
- Adenosine A1/A2 receptors (indirect evidence from in vivo neuroprotection, no binding constants provided) [2] |
|---|---|
| ln Vitro |
In human erythrocytes, 2-chloroadenosine entered cells via a saturable nucleoside transport system with an apparent \(K_m\) of 23 μM and \(V_{max}\) of 24.1 mmol/L cells per hour at 22°C. The transport rate at saturating concentration (1 mM) was 24.2 ± 4.9 mmol/L cells per hour, which was slower than uridine (94.9 ± 1.4 at 2 mM) and adenosine (43.4 ± 4.2 at 1 mM) [1].
- 2-Chloroadenosine uptake was inhibited by nitrobenzylthioinosine, uridine, and adenosine, but not by adenine. Adenosine was a more effective inhibitor (IC50 ~0.18 mM) than uridine (IC50 ~0.60 mM) at 50 μM 2-chloroadenosine [1]. - 2-Chloroadenosine competitively inhibited uridine influx (apparent \(K_i\) = 33 μM) and high-affinity NBMPR binding (apparent \(K_i\) = 0.18 mM) in human erythrocytes [1]. - Preloading human erythrocytes with 5 mM uridine or 5 mM 2-chloroadenosine caused countertransport of [³H]2-chloroadenosine, resulting in a transient 3-fold higher intracellular concentration (0.55 mmol/L cell water) than extracellular (0.20 mM). Adenine preloading had no effect [1]. - In dog erythrocytes (which lack a functional nucleoside transporter), 2-chloroadenosine uptake was slow and linear with concentration (0-4 mM) and not inhibited by NBMPR [1]. |
| ln Vivo |
In a rat model of incomplete forebrain ischemia (10 min bilateral carotid ligation + hypotension), iterative focal hippocampal injections of 2-chloroadenosine (15 nmol in 1 μL phosphate buffer per injection) protected against delayed CA1 pyramidal neuron loss assessed at 7 days reperfusion. When injections were given immediately before ischemia and at 4 and 10 h reperfusion, the 2-chloroadenosine-injected hippocampus had 186 ± 44 neurons vs. 43 ± 5 on the buffer-injected side (p < 0.01), representing ~55% loss on the protected side compared to normal (412 ± 8) [2].
- When the first injection was given at 1 min after ischemia (followed by 4 and 10 h reperfusion), the 2-chloroadenosine side had 369 ± 37 neurons vs. 94 ± 49 on buffer side (p < 0.01), indicating near-total protection [2]. - When injections were delayed to 10 and 24 h reperfusion, no significant protection was observed: 252 ± 46 neurons on 2-chloroadenosine side vs. 233 ± 46 on buffer side (not significant) [2]. |
| Cell Assay |
Human erythrocyte uptake experiments: Fresh human erythrocytes were washed and suspended in buffer. Uptake of [³H]2-chloroadenosine was measured at 22°C by mixing cell suspension (20% hematocrit) with radioactive nucleoside. For rapid fluxes (2-30 sec), uptake was terminated by an inhibitor-oil-stop method using ice-cold stopper medium containing 10 μM nitrobenzylthioguanosine layered over di-n-butyl phthalate, followed by centrifugation. Blank values were obtained by processing cells exposed to labeled nucleoside and 10 μM NBTGR at 0°C. For slower fluxes in dog erythrocytes, cells were washed four times with ice-cold medium [1].
- Countertransport experiments: Human erythrocytes were preloaded with 5 mM unlabeled 2-chloroadenosine, uridine, or adenine for 30 min at 22°C, then washed free of extracellular test compound and resuspended in [³H]2-chloroadenosine (0.20 mM). The appearance of cell-associated radioactivity was measured over time [1]. - Inhibition studies: Various concentrations of inhibitors (adenosine, uridine, adenine) were added simultaneously with 50 μM [³H]2-chloroadenosine to human erythrocytes, and uptake was measured [1]. |
| Animal Protocol |
Rat model of forebrain ischemia: Male Wistar rats (150-200 g) were anesthetized with Nembutal (45 mg/kg i.p.). One week prior to ischemia, bilateral guide cannulae were stereotaxically implanted onto the cortical surface above the hippocampus (coordinates: 3.4 mm anterior to interaural line, 2.5 mm lateral to midline). On the experimental day, rats were anesthetized, paralyzed with suxamethonium chloride (20 mg/kg i.v.), and ventilated with 70% N₂O / 30% O₂. Incomplete forebrain ischemia was induced by bilateral carotid ligation combined with hypotension to maintain mean arterial blood pressure >50 mmHg, continued for 10 min until EEG became isoelectric. Reperfusion was initiated by releasing carotid occlusions and reinfusing withdrawn blood to maintain MABP >100 mmHg [2].
- Drug administration: 2-Chloroadenosine (15 nmol in 1 μL phosphate buffer, pH 7.4) was injected focally into one hippocampus via the guide cannula. The contralateral hippocampus received an equal volume of phosphate buffer. Three injection regimens were tested: (i) immediately before ischemia, then at 4 h and 10 h reperfusion; (ii) at 1 min, 4 h, and 10 h reperfusion; (iii) at 10 h and 24 h reperfusion. Control animals received buffer injections only [2]. - Post-ischemic care: Upon resumption of independent respiration (30-60 min), rats received diazepam (0.4 mg/kg i.v.) to alleviate stress and were allowed to breathe O₂-enriched air until locomotor activity returned (60-120 min) [2]. - Histology: After 7 days, brains were fixed by perfusion with FAM fixative under Nembutal anesthesia (45 mg/kg i.v.), embedded in paraffin, cut into 10 μm coronal sections, and stained with Cresyl violet. CA1 neurons were counted under light microscopy at 4.0 and 3.2 mm anterior to the interaural line along a 470 μm ocular grid at 640× magnification [2]. |
| References | |
| Additional Infomation |
(2R,3R,4S,5R)-2-(6-amino-2-chloro-9-purinyl)-5-(hydroxymethyl)oxacyclopentane-3,4-diol is a purine nucleoside. 2-Chloroadenosine has been reported in Cordyceps sinensis, and relevant data are available. 2-Chloroadenosine is a metabolically stable adenosine analog that functions as an adenosine receptor agonist. This compound has significant effects on both the peripheral and central nervous systems.
2-Chloroadenosine is a stable adenosine analogue that is resistant to deamination by adenosine deaminase, but can be phosphorylated by adenosine kinase [1]. - It acts as a permeant substrate for the nucleoside transporter in human erythrocytes, contradicting the earlier assumption that it is not transported. The inability of nucleoside transport inhibitors to potentiate its pharmacological effects may be due to kinetic factors rather than lack of transport [1]. - In the rat brain, 2-chloroadenosine protects hippocampal CA1 neurons from ischemic delayed cell death when administered early (within 1 min post-ischemia), but not when delayed to 10-24 h. The protective mechanism may involve presynaptic inhibition of excitatory amino acid (aspartate, glutamate) release and postsynaptic blockade of Ca²⁺ spikes and burst firing, thereby attenuating excitotoxicity [2]. |
| Molecular Formula |
C10H12CLN5O4
|
|---|---|
| Molecular Weight |
301.687
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| Exact Mass |
301.057
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| CAS # |
146-77-0
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| PubChem CID |
8974
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| Appearance |
White to off-white solid powder
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| Density |
2.2±0.1 g/cm3
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| Boiling Point |
643.3±65.0 °C at 760 mmHg
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| Melting Point |
162 °C
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| Flash Point |
342.8±34.3 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
|
| Index of Refraction |
1.912
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| LogP |
-0.46
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| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
367
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O)O)Cl)N
|
| InChi Key |
BIXYYZIIJIXVFW-UUOKFMHZSA-N
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| InChi Code |
InChI=1S/C10H12ClN5O4/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,14,15)/t3-,5-,6-,9-/m1/s1
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| Chemical Name |
(2R,3R,4S,5R)-2-(6-amino-2-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
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| Synonyms |
BRN 0043957 BRN-0043957BRN0043957 NSC36896 NSC-36896NSC 36896
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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 (~331.47 mM)
H2O : ~33.33 mg/mL (~110.48 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.29 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 25.0 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: ≥ 2.5 mg/mL (8.29 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 25.0 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: ≥ 2.5 mg/mL (8.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 18.75 mg/mL (62.15 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3147 mL | 16.5733 mL | 33.1466 mL | |
| 5 mM | 0.6629 mL | 3.3147 mL | 6.6293 mL | |
| 10 mM | 0.3315 mL | 1.6573 mL | 3.3147 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05263284 | RECRUITING | Drug: 8-Chloroadenosine Drug: Venetoclax |
Acute Myeloid Leukemia Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia |
City of Hope Medical Center | 2022-12-15 | Phase 1 |
| NCT02509546 | COMPLETEDWITH RESULTS | Drug: 8-Chloroadenosine Other: Laboratory Biomarker Analysis Other: Pharmacological Study |
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia |
City of Hope Medical Center | 2015-09-02 | Phase 1 Phase 2 |
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