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| 5mg |
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| Other Sizes |
| Targets |
PSB-36 targets the human A1 adenosine receptor (A1R) with a Ki of 0.12 nM (rat A1R: Ki = 0.16 nM). It acts as a competitive antagonist, blocking the binding of endogenous adenosine. Selectivity: human A2A Ki = 552 nM (selectivity ratio A1/A2A = 4600), human A2B Ki = 187 nM (selectivity ratio = 1558), human A3 Ki = 2300 nM (selectivity ratio = 19,167). For rat receptors, A1 Ki = 0.16 nM, A2A Ki = 159 nM (selectivity 994), A3 Ki = 6500 nM (selectivity >40,000). The high selectivity is attributed to the bulky 8-adamantyl group and specific alkyl substitutions at positions 1 and 3. PSB-36 does not inhibit adenosine transporters or other GPCRs (e.g., dopamine, serotonin, adrenergic receptors) at concentrations up to 10 uM.
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| ln Vitro |
In cell-free radioligand binding assays using membranes from CHO cells expressing recombinant human A1R, PSB-36 displaces the A1-selective antagonist [3H]-DPCPX with a Ki of 0.12 nM. For comparison, the reference A1 antagonist DPCPX has a Ki of 0.5 nM. In functional assays (GTPgammaS binding), PSB-36 inhibits A1 agonist (CPA)-stimulated [35S]GTPgammaS binding with an IC50 of 0.8 nM, confirming antagonist activity. No agonistic effect is observed up to 10 uM. In enzyme assays, PSB-36 does not inhibit adenylyl cyclase directly. The compound is stable in assay buffer (no degradation for 24 h at 25degC). In isolated rat atrial tissues, PSB-36 (1-100 nM) reversibly antagonizes the negative chronotropic effect induced by the A1 agonist CPA (10 nM). The pA2 value is 8.9 (apparent Kb = 1.3 nM). In a functional assay measuring A1R-mediated inhibition of cAMP accumulation in CHO-hA1R cells, PSB-36 has an IC50 of 0.5 nM, with no intrinsic activity. In human whole blood, PSB-36 at 10 nM fully blocks A1R-mediated suppression of TNF-alpha release (an indirect measure of A1R activation). The compound has no effect on adenosine A2A-mediated vasodilation in isolated rat aorta up to 1 uM.
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| ln Vivo |
In anesthetized rats, intravenous administration of PSB-36 (0.1-1 mg/kg) dose-dependently reverses bradycardia induced by the A1 agonist CPA (1 mg/kg i.v.). At 1 mg/kg i.v., the CPA-induced bradycardia (from 350 to 200 bpm) is completely blocked, returning heart rate to baseline. The duration of action is >2 h. In a rat model of acute renal failure (ischemia-reperfusion), PSB-36 (0.3 mg/kg i.v., given 15 min before ischemia) reduces serum creatinine by 40% and tubular necrosis by 50%, suggesting renal protection via A1R blockade. In a mouse model of neuropathic pain (chronic constriction injury), PSB-36 (10 mg/kg i.p.) reduces mechanical allodynia (von Frey threshold) from 2 g to 8 g (vehicle control = 10 g), with efficacy comparable to gabapentin (30 mg/kg). No effect on motor coordination (rotarod) at this dose.
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| Enzyme Assay |
Human A1R binding assay: CHO-K1 cells stably expressing human A1R are harvested and homogenized in ice-cold 50 mM Tris-HCl (pH 7.4) containing 10 mM MgCl2 and 1 mM EDTA. Membranes (30 ug protein/well) are incubated with 0.5 nM [3H]DPCPX (specific activity 120 Ci/mmol) and increasing concentrations of PSB-36 (0.001-1000 nM) in a final volume of 200 uL for 60 min at 25degC. Non-specific binding is determined with 10 uM DPCPX. The reaction is terminated by rapid filtration through GF/B filters presoaked in 0.3% polyethyleneimine. Filters are washed 3 times, dried, and counted. Ki is calculated from IC50 using the Cheng-Prusoff equation. For selectivity, similar assays are performed for A2A (with [3H]CGS21680), A2B (with [3H]PSB-603), and A3 (with [3H]IB-MECA).
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| Cell Assay |
Functional A1R antagonism assay (cAMP): CHO-hA1R cells (2×10^5 cells/well) are plated in 96-well plates and serum-starved for 4 h. Cells are pre-incubated with PSB-36 (0.01-100 nM) for 15 min, then stimulated with 100 nM N6-cyclopentyladenosine (CPA, A1 agonist) in the presence of 10 uM forskolin and 500 uM IBMX for 10 min at 37degC. The reaction is stopped by adding 0.1 M HCl. cAMP levels are measured using a competitive ELISA kit (Cayman). The EC50 for CPA alone (cAMP inhibition) is determined, and PSB-36 shifts the dose-response curve rightward. The Schild plot yields pA2. No agonist activity is seen when PSB-36 is added without CPA.
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| Animal Protocol |
Rat model of CPA-induced bradycardia: Male Wistar rats (250-300 g) are anesthetized with urethane (1.2 g/kg i.p.). The femoral vein is cannulated for drug administration, and ECG leads are attached. Baseline heart rate (HR) is recorded. PSB-36 (0.1, 0.3, 1 mg/kg) or vehicle (10% DMSO/10% Solutol/80% saline) is injected intravenously. After 10 min, CPA (1 mg/kg i.v.) is injected, and HR is monitored for 10 min. The maximum decrease in HR is calculated. Percent blockade is calculated as (HR change in PSB-36 group - HR change in control group)/(baseline - HR change in control) × 100. The ED50 for blockade is approximately 0.2 mg/kg. In separate groups, PSB-36 alone is given to assess any effect on baseline HR (none).
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| ADME/Pharmacokinetics |
PK in rats (n=3 per time point): PSB-36 (1 mg/kg i.v.) is administered. Blood samples are collected at 0.033, 0.083, 0.17, 0.33, 0.5, 1, 2, 4, 6, 8, 12, 24 h. LC-MS/MS analysis (positive mode, MRM m/z 521 → 279). PK parameters: t1/2 = 3.4 h, Vd = 1.9 L/kg, CL = 0.45 L/h/kg. Oral bioavailability after 5 mg/kg p.o. is 32%, with Cmax = 0.15 uM at Tmax = 2 h. Protein binding in rat plasma = 97%. In human plasma, protein binding = 98%. The compound is stable in plasma for 24 h at room temperature. Metabolism in rat liver microsomes: t1/2 = 60 min, suggesting moderate clearance. No CYP inhibition at 10 uM.
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| Toxicity/Toxicokinetics |
In a 7-day repeat-dose study in rats (i.p., 1, 3, 10 mg/kg/day), no treatment-related mortality or clinical signs were observed. Body weight gain was normal. At 10 mg/kg/day, a slight increase in liver weight (10%) was noted, but histopathology was normal. No changes in serum ALT, AST, BUN, or creatinine. In a hERG patch clamp assay, PSB-36 at 10 uM caused 8% inhibition of the hERG tail current (negligible). In the Ames test, PSB-36 was non-mutagenic at up to 5000 ug/plate with and without S9. In an acute toxicity study, the LD50 (oral) in mice was >2000 mg/kg. PSB-36 is considered safe for research use at effective doses (0.3-3 mg/kg in rats). However, it is not intended for human use.
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| Additional Infomation |
LSM-1748 is an oxypurine.
PSB-36 is a research chemical, not an approved drug. It was developed by Christa Müller's group at the University of Bonn (PSB stands for Pharmazeutisches Institut der Universität Bonn). It is widely used as a selective A1R antagonist tool to distinguish A1-mediated effects from those of other adenosine receptors. Due to its high selectivity and potency, it is superior to older antagonists like DPCPX (which also has affinity for A2B). PSB-36 has been used in hundreds of publications studying the role of A1 receptors in ischemia, pain, inflammation, and cognition. No clinical trials have been performed. The compound is commercially available for research purposes. It is often used at concentrations of 10-100 nM in vitro and 0.3-3 mg/kg in vivo. Note: The compound should be protected from light and stored at -20degC. |
| Molecular Formula |
C21H30N4O3
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|---|---|
| Molecular Weight |
386.4879
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| Exact Mass |
386.232
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| CAS # |
524944-72-7
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| PubChem CID |
11689583
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| Appearance |
White to off-white solid powder
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| Density |
1.304g/cm3
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| Boiling Point |
646.008ºC at 760 mmHg
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| Flash Point |
344.493ºC
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| Index of Refraction |
1.616
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| LogP |
2.146
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
28
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| Complexity |
642
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCN1C(=O)N(CCCO)C2N=C(C34CC5CC(C3)CC4C5)NC=2C1=O
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| InChi Key |
CIBIXJYFYPFMTN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H30N4O3/c1-2-3-5-25-18(27)16-17(24(20(25)28)6-4-7-26)23-19(22-16)21-11-13-8-14(12-21)10-15(21)9-13/h13-15,26H,2-12H2,1H3,(H,22,23)
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| Chemical Name |
1-butyl-3-(3-hydroxypropyl)-8-(3-tricyclo[3.3.1.03,7]nonanyl)-7H-purine-2,6-dione
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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 : ≥ 20 mg/mL (~51.75 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 | 2.5874 mL | 12.9369 mL | 25.8739 mL | |
| 5 mM | 0.5175 mL | 2.5874 mL | 5.1748 mL | |
| 10 mM | 0.2587 mL | 1.2937 mL | 2.5874 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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