| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Ki: 6.05 µM (PKA I) and 9.75 µM (PKA II)[1]
The primary target of Rp-cAMPS sodium salt is protein kinase A (PKA), both type I and type II holoenzymes. It binds competitively to the cAMP-binding domains on the regulatory subunits of PKA (RI and RII) with Ki values of 12.5 uM for PKA I and 4.5 uM for PKA II. It acts as a competitive antagonist, binding to the same site as cAMP but failing to induce the conformational change required for catalytic subunit dissociation. It has no significant affinity for Epac proteins (exchange proteins directly activated by cAMP). |
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| ln Vitro |
By attaching to regulatory subunits without dissociating the kinase holoenzyme, a membrane-permeable competitive cAMP antagonist (Rp-cAMPS) inhibits PKA activation and suppresses synaptic plasticity while having no effect on regular synaptic transmission. [2].
In vitro, Rp-cAMPS sodium salt potently and competitively inhibits PKA activation with Ki values of 12.5 uM (PKA type I) and 4.5 uM (PKA type II). In cell-free assays using purified PKA holoenzyme, the compound blocks cAMP-stimulated kinase activity with an IC50 typically in the low micromolar range. In cell homogenates, it strongly inhibits cAMP-dependent protein kinase activity. It does not activate Epac or other cAMP-binding proteins, making it a highly selective PKA antagonist. It is often used in combination with Sp-cAMPS (PKA activator) to dissect signaling pathways. |
| ln Vivo |
In slices from arthritic rats, monosynaptic EPSCs triggered by PB-CeLC and BLA-CelC synapses are reduced by Rp-cAMPS sodium salt (10 μM, 15 min), but control neurons from normal animals are not affected. When comparing Rp-cAMPS sodium salt's inhibitory impact to pre-drug (ACSF) control values found in the same neurons, a significant difference was seen [2].
Although typically used in cell-based systems, Rp-cAMPS sodium salt has been administered in vivo in animal models, particularly in cardiovascular, neurological, and metabolic research. For example, it has been used in rats to study the role of PKA in cardiac contractility: intravenous infusion (1-10 mg/kg) reversed cAMP-induced positive inotropic effects. In mouse models of long-term memory, intrahippocampal injection of Rp-cAMPS (10-50 uM) impaired memory consolidation in fear conditioning assays. In pancreatic beta cells, microinjection or perfusion of Rp-cAMPS (100 uM) inhibited insulin secretion induced by glucagon-like peptide-1 (GLP-1) or forskolin. |
| Enzyme Assay |
Standard protocol for evaluating PKA inhibition in a cell-free system: Prepare a reaction mix containing 50 uL of PKA holoenzyme (0.1 ug) in 20 mM Tris-HCl pH 7.4, 5 mM MgCl2, 0.1 mg/mL BSA. Add various concentrations of Rp-cAMPS sodium salt (0.1-1000 uM) and incubate for 10 minutes at 30degC. Then add 100 uM cAMP and the peptide substrate (e.g., kemptide, LRRASLG, 50 uM) along with 100 uM ATP containing 1 uCi [gamma-32P]-ATP. Incubate for 10 minutes. Spot 20 uL onto P81 phosphocellulose paper, wash 3 times with 0.75% phosphoric acid, and measure incorporated radioactivity by scintillation counting. IC50 is calculated by nonlinear regression. Ki is determined from competition curves.
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| Cell Assay |
For cell-based assays: HEK293T, HeLa, or primary neurons are seeded in 6-well plates (1×10⁶ cells/well) and cultured to 70-80% confluency. The day before the experiment, cells are transfected with a PKA activity reporter (e.g., FRET-based AKAR, or CRE-luciferase reporter). Cells are pre-incubated with Rp-cAMPS (10-500 uM) for 30-60 minutes, then stimulated with a cAMP agonist (e.g., 1-10 uM forskolin, 100 uM 8-Br-cAMP, or 10 uM isoproterenol). PKA activity is measured by live-cell FRET imaging or by lysing cells and measuring luciferase activity. For Western blot analysis, cells are lysed in RIPA buffer with phosphatase inhibitors, and phosphorylated PKA substrates (e.g., p-CREB Ser133) are detected using phospho-specific antibodies. Cyclic AMP analogs for PKA activation study via kinase activity assessment.
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| Animal Protocol |
For in vivo experiments: Male Sprague-Dawley rats (250-300 g) are anesthetized with isoflurane. For studies of cardiac function, Rp-cAMPS is administered intravenously via a jugular vein catheter as a bolus of 1-10 mg/kg. Cardiac contractility is measured by left ventricular pressure-volume loops using a conductance catheter. Alternatively, for memory studies, mice (C57BL/6) are surgically implanted with bilateral guide cannulae aimed at the dorsal hippocampus. After recovery, mice undergo fear conditioning training. Immediately after training, Rp-cAMPS (dissolved in artificial CSF, 5 ug/side in 0.5 uL) is infused over 2 minutes via injection needles inserted through the guide cannulae. Memory is tested 24 hours later by measuring freezing behavior to the conditioning context. Control animals receive vehicle (aCSF) or Sp-cAMPS.
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| ADME/Pharmacokinetics |
In vivo pharmacokinetic data for Rp-cAMPS sodium salt are limited. The compound is cell-permeable but polar, limiting passive diffusion across biological membranes. Systemic administration requires high doses due to rapid clearance and potential metabolism by phosphodiesterases (PDEs). Peak plasma concentrations after IV administration are reached quickly, but the half-life is short (estimated 30-60 minutes) due to rapid excretion and metabolism. The compound may be dephosphorylated by tissue phosphatases or converted to the corresponding nucleoside. No oral bioavailability data are available, and it is typically administered by injection or direct tissue infusion. It is soluble in water and in DMSO.
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| Toxicity/Toxicokinetics |
Rp-cAMPS sodium salt has low acute toxicity in vivo at the typical experimental doses used (1-10 mg/kg IV or 5-50 ug intracerebral). At higher doses (>20 mg/kg IV), it may cause hypotension, bradycardia, and neurological effects. No formal LD50 or chronic toxicity studies have been published. The compound is not classified as a mutagen or carcinogen. As a laboratory chemical, it should be handled with standard precautions (gloves, lab coat, eye protection). The compound is stable for several years when stored as a powder at -20degC and protected from light. Solutions in water or DMSO should be stored at -20degC and used within 6 months.
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| References |
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| Additional Infomation |
Rp-cAMPS sodium salt is not an approved drug and has not undergone clinical trials for therapeutic use. It is exclusively a research tool for cell signaling studies. It is often used in combination with its diastereomer, Sp-cAMPS (a PKA activator), to demonstrate the specificity of PKA-mediated effects. The compound is referenced in thousands of scientific publications as a standard PKA inhibitor. Its chemical modification (phosphorothioate backbone) confers resistance to degradation by phosphodiesterases (PDEs), making it more stable in cells and tissues compared to natural cAMP. While not a drug itself, understanding its mechanism has guided the development of therapeutic PKA modulators for diseases such as cystic fibrosis, cardiac hypertrophy, and memory disorders. The compound is available from multiple chemical vendors for research use only.
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| Molecular Formula |
C10H11N5NAO5PS
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|---|---|
| Molecular Weight |
367.25
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| Exact Mass |
367.011
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| CAS # |
142439-94-9
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| Related CAS # |
Rp-cAMPS triethylammonium salt;151837-09-1;Sp-cAMPS sodium salt;142439-95-0;Rp-cAMPS;73208-40-9
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| PubChem CID |
23682235
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| Appearance |
White to pink solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
23
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| Complexity |
508
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1[C@@H]2[C@H]([C@H]([C@@H](O2)N3C=NC4=C(N=CN=C43)N)O)OP(=S)(O1)[O-].[Na+]
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| InChi Key |
YTUKZYORDGLGPR-NVGWRVNNSA-M
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| InChi Code |
InChI=1S/C10H12N5O5PS.Na/c11-8-5-9(13-2-12-8)15(3-14-5)10-6(16)7-4(19-10)1-18-21(17,22)20-7;/h2-4,6-7,10,16H,1H2,(H,17,22)(H2,11,12,13);/q;+1/p-1/t4-,6-,7-,10-,21?;/m1./s1
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| Chemical Name |
sodium;(4aR,6R,7R,7aS)-6-(6-aminopurin-9-yl)-2-oxido-2-sulfanylidene-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-7-ol
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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 and light. |
| 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) |
H2O: 250 mg/mL (680.74 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (272.29 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7229 mL | 13.6147 mL | 27.2294 mL | |
| 5 mM | 0.5446 mL | 2.7229 mL | 5.4459 mL | |
| 10 mM | 0.2723 mL | 1.3615 mL | 2.7229 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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