Home >> Research Area >>MAPK Signaling>>cAMP>> cAMPS-Rp, triethylammonium salt

cAMPS-Rp, triethylammonium salt

cAMP antagonist; inhibits PKA activation CAS# 151837-09-1

cAMPS-Rp, triethylammonium salt

Catalog No. BCC8082----Order now to get a substantial discount!

Product Name & Size Price Stock
cAMPS-Rp, triethylammonium salt:1mg $158.00 In stock
cAMPS-Rp, triethylammonium salt:2mg $269.00 In stock
cAMPS-Rp, triethylammonium salt:5mg $632.00 In stock
cAMPS-Rp, triethylammonium salt:10mg $1106.00 In stock
Related Products

Quality Control of cAMPS-Rp, triethylammonium salt

Number of papers citing our products

Chemical structure

cAMPS-Rp, triethylammonium salt

3D structure

Chemical Properties of cAMPS-Rp, triethylammonium salt

Cas No. 151837-09-1 SDF Download SDF
PubChem ID 5311365 Appearance Powder
Formula C16H27N6O5PS M.Wt 446.46
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 100 mM in water
Chemical Name (R)-Adenosine, cyclic 3',5'-(hydrogenphosphorothioate) triethylammonium
SMILES CCN(CC)CC.C1C2C(C(C(O2)N3C=NC4=C3N=CN=C4N)O)OP(=S)(O1)O
Standard InChIKey FKAWLXNLHHIHLA-YCBIHMBMSA-N
Standard InChI InChI=1S/C50H81N4O15P/c1-29(20-22-51)16-14-17-30(2)32(4)24-33(5)42(57)35(7)38(55)25-41(65-13)45-46(69-70(61,62)63)49(8,9)50(68-45)26-39(56)34(6)40(67-50)19-15-18-36-27-66-48(53-36)31(3)21-23-52-47(60)44(59)43(58)37(28-64-12)54(10)11/h14-18,20,24,27,31,33-35,37-46,55-59H,19,21,23,25-26,28H2,1-13H3,(H,52,60)(H2,61,62,63)/b16-14+,18-15+,29-20-,30-17+,32-24+/t31-,33+,34-,35-,37-,38-,39+,40-,41-,42+,43-,44-,45+,46-,50+/m0/s1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of cAMPS-Rp, triethylammonium salt

DescriptionCell-permeable cAMP analog; acts as a competitive antagonist of cAMP-induced activation of PKA (IC50 = 11 - 16 μM) by interacting with cAMP binding sites on the regulatory subunits. Resistant to hydrolysis by phosphodiesterases. Enantiomer cAMPS-Sp, triethylammonium salt also available.

cAMPS-Rp, triethylammonium salt Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

cAMPS-Rp, triethylammonium salt Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of cAMPS-Rp, triethylammonium salt

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.2398 mL 11.1992 mL 22.3984 mL 44.7968 mL 55.9961 mL
5 mM 0.448 mL 2.2398 mL 4.4797 mL 8.9594 mL 11.1992 mL
10 mM 0.224 mL 1.1199 mL 2.2398 mL 4.4797 mL 5.5996 mL
50 mM 0.0448 mL 0.224 mL 0.448 mL 0.8959 mL 1.1199 mL
100 mM 0.0224 mL 0.112 mL 0.224 mL 0.448 mL 0.56 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University
Featured Products
New Products
 

References on cAMPS-Rp, triethylammonium salt

The P2Y12 antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt and cangrelor (ARC69931MX), can inhibit human platelet aggregation through a Gi-independent increase in cAMP levels.[Pubmed:19346255]

J Biol Chem. 2009 Jun 12;284(24):16108-17.

ADP plays an integral role in the process of hemostasis by signaling through two platelet G-protein-coupled receptors, P2Y1 and P2Y12. The recent use of antagonists against these two receptors has contributed a substantial body of data characterizing the ADP signaling pathways in human platelets. Specifically, the results have indicated that although P2Y1 receptors are involved in the initiation of platelet aggregation, P2Y12 receptor activation appears to account for the bulk of the ADP-mediated effects. Based on this consideration, emphasis has been placed on the development of a new class of P2Y12 antagonists (separate from clopidogrel and ticlopidine) as an approach to the treatment of thromboembolic disorders. The present work examined the molecular mechanisms by which two of these widely used adenosine-based P2Y12 antagonists (2-methylthioadenosine 5'-monophosphate triethylammonium salt (2MeSAMP) and ARC69931MX), inhibit human platelet activation. It was found that both of these compounds raise platelet cAMP to levels that substantially inhibit platelet aggregation. Furthermore, the results demonstrated that this elevation of cAMP did not require Gi signaling or functional P2Y12 receptors but was mediated through activation of a separate G protein-coupled pathway, presumably involving Gs. However, additional experiments revealed that neither 2MeSAMP nor ARC69931MX (cangrelor) increased cAMP through activation of A2a, IP, DP, or EP2 receptors, which are known to couple to Gs. Collectively, these findings indicate that 2MeSAMP and ARC69931MX interact with an unidentified platelet G protein-coupled receptor that stimulates cAMP-mediated inhibition of platelet function. This inhibition is in addition to that derived from antagonism of P2Y12 receptors.

Detecting proton flux across chromatophores driven by F0F1-ATPase using N-(fluorescein-5-thiocarbamoyl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolami ne, triethylammonium salt.[Pubmed:16043113]

Anal Biochem. 2005 Sep 1;344(1):102-7.

N-(Fluorescein-5-thiocarbamoyl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolami ne, triethylammonium salt (F-DHPE) is a lipid fluorescence dye sensitive to pH changes and is used in this study for detecting proton flux through F0F1-ATPase within chromatophores driven by ATP hydrolysis. F-DHPE is easily labeled to the outer surface of chromatophores. In the range of pH 7.0 to 9.0, fluorescence intensity is sensitive to pH changes. The sensitivity is especially great in the range of pH 8.2 to 9.0, so pH 8.6 was chosen as the appropriate experimental condition. It is shown that added ATP not only acts as a fluorescence quencher but also can be hydrolyzed by F0F1-ATPase to pump protons into chromatophores, resulting in fluorescence restoration. A stimulator (NaSO3) and various types of inhibitors (NaN3, 5'-adenylyl imidodiphosphate [AMP-PNP], and N,N'-dicyclohexylcarbodiimide [DCCD]) of F0F1 confirmed that fluorescence restoration is caused by ATP-driven proton flux. When loaded with one antibody (anti-beta antibody) or two antibodies (anti-beta antibody and sheep to rabbit second antibody), F0F1-ATPase exhibits lower proton pumping activities, as indicated by fluorescence restoration. The possible mechanism of the inhibition of antibodies on proton pumping activity is discussed.

Synthesis of gemcitabine triphosphate (dFdCTP) as a tris(triethylammonium) salt.[Pubmed:18396042]

Bioorg Med Chem Lett. 2008 May 1;18(9):2957-8.

First synthesis of gemcitabine triphosphate (dFdCTP) as a tris(triethylammonium) salt is reported.

Receptor-independent effects of 2'(3')-O-(4-benzoylbenzoyl)ATP triethylammonium salt on cytosolic pH.[Pubmed:23689980]

Purinergic Signal. 2013 Dec;9(4):687-93.

The effect of the relatively potent P2X7 receptor agonist 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate triethylammonium salt (BzATP-TEA) on cytosolic pH (pHi) was studied using MC3T3-E1 osteoblast-like cells, which endogenously express P2X7 receptors. pHi was measured fluorimetrically using the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. BzATP-TEA (0.3-1.5 mM) elicited fast-onset alkalinization responses. In contrast, adenosine 5'-triphosphate disodium salt (5 mM) failed to reproduce the BzATP-TEA-induced responses, indicating a P2 receptor-independent mechanism. We speculated that triethylamine, which is present in solutions of BzATP-TEA, permeates the plasma membrane, and is protonated intracellularly, leading to an increase in pHi. Consistent with this hypothesis, triethylammonium (TEA) chloride mimicked the effects of BzATP-TEA on pHi. Moreover, measurements using a Cytosensor microphysiometer revealed that TEA chloride transiently suppressed proton efflux from cells, whereas washout of TEA transiently enhanced proton efflux. BzATP-TEA also elicited a sustained increase in proton efflux that was blocked specifically by the P2X7 antagonist A-438079. Taken together, we conclude that BzATP-TEA-induced alkalinization is unrelated to P2X7 activation, but is due to the presence of TEA. This effect may confound assessment of the outcomes of P2X7 activation by BzATP-TEA in other systems. Thus, control experiments using TEA chloride are recommended to distinguish between receptor-mediated and nonspecific effects of this widely used agonist. We performed such a control and confirmed that BzATP-TEA, but not TEA chloride, caused the elevation of cytosolic free Ca(2+) in MC3T3-E1 cells, ruling out the possibility that receptor-independent effects on pHi underlie BzATP-TEA-induced Ca(2+) signaling.

Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats.[Pubmed:25849133]

Nat Med. 2015 May;21(5):506-11.

Metformin is a first-line therapeutic option for the treatment of type 2 diabetes, even though its underlying mechanisms of action are relatively unclear. Metformin lowers blood glucose levels by inhibiting hepatic glucose production (HGP), an effect originally postulated to be due to a hepatic AMP-activated protein kinase (AMPK)-dependent mechanism. However, studies have questioned the contribution of hepatic AMPK to the effects of metformin on lowering hyperglycemia, and a gut-brain-liver axis that mediates intestinal nutrient- and hormone-induced lowering of HGP has been identified. Thus, it is possible that metformin affects HGP through this inter-organ crosstalk. Here we show that intraduodenal infusion of metformin for 50 min activated duodenal mucosal Ampk and lowered HGP in a rat 3 d high fat diet (HFD)-induced model of insulin resistance. Inhibition of duodenal Ampk negated the HGP-lowering effect of intraduodenal metformin, and both duodenal glucagon-like peptide-1 receptor (Glp-1r)-protein kinase A (Pka) signaling and a neuronal-mediated gut-brain-liver pathway were required for metformin to lower HGP. Preabsorptive metformin also lowered HGP in rat models of 28 d HFD-induced obesity and insulin resistance and nicotinamide (NA)-streptozotocin (STZ)-HFD-induced type 2 diabetes. In an unclamped setting, inhibition of duodenal Ampk reduced the glucose-lowering effects of a bolus metformin treatment in rat models of diabetes. These findings show that, in rat models of both obesity and diabetes, metformin activates a previously unappreciated duodenal Ampk-dependent pathway to lower HGP and plasma glucose levels.

PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic plasticity and behavior.[Pubmed:18631385]

Mol Pain. 2008 Jul 16;4:26.

The laterocapsular division of the central nucleus of the amygdala (CeLC) has emerged as an important site of pain-related plasticity and pain modulation. Glutamate and neuropeptide receptors in the CeLC contribute to synaptic and behavioral changes in the arthritis pain model, but the intracellular signaling pathways remain to be determined. This study addressed the role of PKA, PKC, and ERK in the CeLC. Adult male Sprague-Dawley rats were used in all experiments. Whole-cell patch-clamp recordings of CeLC neurons were made in brain slices from normal rats and from rats with a kaolin/carrageenan-induced monoarthritis in the knee (6 h postinduction). Membrane-permeable inhibitors of PKA (KT5720, 1 microM; cAMPS-Rp, 10 microM) and ERK (U0126, 1 microM) activation inhibited synaptic plasticity in slices from arthritic rats but had no effect on normal transmission in control slices. A PKC inhibitor (GF109203x, 1 microM) and an inactive structural analogue of U0126 (U0124, 1 microM) had no effect. The NMDA receptor-mediated synaptic component was inhibited by KT5720 or U0126; their combined application had additive effects. U0126 did not inhibit synaptic facilitation by forskolin-induced PKA-activation. Administration of KT5720 (100 microM, concentration in microdialysis probe) or U0126 (100 microM) into the CeLC, but not striatum (placement control), inhibited audible and ultrasonic vocalizations and spinal reflexes of arthritic rats but had no effect in normal animals. GF109203x (100 microM) and U0124 (100 microM) did not affect pain behavior. The data suggest that in the amygdala PKA and ERK, but not PKC, contribute to pain-related synaptic facilitation and behavior by increasing NMDA receptor function through independent signaling pathways.

Isoproterenol inhibits rod outer segment phagocytosis by both cAMP-dependent and independent pathways.[Pubmed:7890503]

Invest Ophthalmol Vis Sci. 1995 Mar;36(3):730-6.

PURPOSE: The authors studied the involvement of cAMP-dependent second messenger systems in the inhibition of rod outer segment (ROS) phagocytosis by isoproterenol (ISO) and forskolin (FSK) using two membrane-permeant analogs of cyclic adenosine monophosphate (cAMP), the Rp and Sp diastereoisomers of cyclic adenosine 3',5' monophosphothioate (cAMPS). Rp-cAMPS is a potent competitive inhibitor of cAMP-dependent protein kinase I and II (PKA I and II), whereas Sp-cAMPS is a potent activator of these enzymes. METHODS: ROS phagocytosis was quantitated in cultured rat RPE cells using a previously described double immunofluorescence assay. RESULTS: Sp-cAMPS showed a dose-dependent inhibition of ROS phagocytosis, whereas 100 microM Rp-cAMPS had no effect on this process. Rp-cAMPS fully prevented the inhibitory effect of Sp-cAMPS and FSK but was able to prevent only partially the inhibition of ROS phagocytosis induced by ISO. Isoproterenol plus FSK showed an additive effect on the inhibition of phagocytosis, suggesting that they act at two independent sites. However, ISO plus Sp-cAMPS or FSK plus Sp-cAMPS showed no additivity. CONCLUSIONS: Results suggest that FSK inhibits ROS phagocytosis by RPE cells through a cAMP-dependent pathway, whereas ISO inhibits ROS phagocytosis by RPE cells through cAMP-dependent and cAMP-independent pathways.

Probing the cyclic nucleotide binding sites of cAMP-dependent protein kinases I and II with analogs of adenosine 3',5'-cyclic phosphorothioates.[Pubmed:2162349]

J Biol Chem. 1990 Jun 25;265(18):10484-91.

A set of cAMP analogs were synthesized that combined exocyclic sulfur substitutions in the equatorial (Rp) or the axial (Sp) position of the cyclophosphate ring with modifications in the adenine base of cAMP. The potency of these compounds to inhibit the binding of [3H]cAMP to sites A and B from type I (rabbit skeletal muscle) and type II (bovine myocardium) cAMP-dependent protein kinase was determined quantitatively. On the average, the Sp isomers had a 5-fold lower affinity for site A and a 30-fold lower affinity for site B of isozyme I than their cyclophosphate homolog. The mean reduction in affinities for the equivalent sites of isozyme II were 20- and 4-fold, respectively. The Rp isomers showed a decrease in affinity of approximately 400-fold and 200-fold for site A and B, respectively, of isozyme I, against 200-fold and 45-fold for site A and B of isozyme II. The Sp substitutions therefore increased the relative preference for site A of isozyme I and site B of isozyme II. The Rp substitution, on the other hand, increased the relative preference for site B of both isozymes. These data show that the Rp and Sp substitutions are tolerated differently by the two intrachain sites of isozymes I and II. They also support the hypothesis that it is the axial, and not the previously proposed equatorial oxygen that contributes the negative charge for the ionic interaction with an invariant arginine in all four binding sites. In addition, they demonstrate that combined modifications in the adenine ring and the cyclic phosphate ring of cAMP can enhance the ability to discriminate between site A and B of one isozyme as well as to discriminate between isozyme I and II. Since Rp analogs of cAMP are known to inhibit activation of cAMP-dependent protein kinases, the findings of the present study have implications for the synthesis of analogs having a very high selectivity for isozyme I or II.

A mechanistic and kinetic analysis of the interactions of the diastereoisomers of adenosine 3',5'-(cyclic)phosphorothioate with purified cyclic AMP-dependent protein kinase.[Pubmed:2843164]

Biochem J. 1988 May 1;251(3):757-62.

The binding affinities of the diastereoisomers of adenosine 3',5'-(cyclic)phosphorothioate, Sp-cAMP[S] and Rp-cAMP[S], for the cyclic AMP- (cAMP-)binding sites on purified and reconstituted pig heart type II cAMP-dependent protein kinase holoenzyme were determined by measuring the ability of these compounds to displace [3H]cAMP from this enzyme. Sp-cAMP[S], a cAMP agonist, displaced 50% of the [3H]cAMP bound to the holoenzyme at a concentration 10-fold higher than that of cAMP; Rp-cAMP[S], a cAMP antagonist, required a 100-fold higher concentration relative to cAMP. Activation of the isolated holoenzyme, determined as phosphotransferase activity, was measured in the presence of the agonist and in the absence and in the presence of increasing concentrations of the antagonist. The results of fitting the activation data to sigmoid curves with a non-linear-regression program and to Hill plots by using a linear-regression program showed that Rp-cAMP[S] had no effect on Vmax, increased the EC50 values for agonist activation and had no effect on the co-operativity of activation (h). A Ki value of 11 microM was determined for Rp-cAMP[S] inhibition of cAMP-induced activation of purified type II cAMP-dependent protein kinase. Electrophoresis of the holoenzyme on polyacrylamide gels under non-denaturing conditions in the presence of saturating concentrations of the diastereoisomers resulted in 100% dissociation of the subunits with Sp-cAMP[S] and 0% dissociation with Rp-cAMP[S]. Sp-cAMP[S], the isomer with an axial exocyclic sulphur atom, binds to the holoenzyme, releases the catalytic subunit and activates the phosphotransferase activity. Rp-cAMP[S], the isomer with an equatorial exocyclic sulphur atom, binds to the holoenzyme but does not result in dissociation, and thus acts as a competitive inhibitor of phosphotransferase activity.

Competitive cAMP antagonists for cAMP-receptor proteins.[Pubmed:6088478]

J Biol Chem. 1984 Aug 25;259(16):10020-4.

The two exocyclic oxygen atoms at phosphorus of cAMP have been replaced by a sulfur atom or by a dimethylamino group. These substitutions introduce chirality at the phosphorus atom; therefore, two diastereoisomers are known for each derivative: (SP)-cAMPS, (RP)-cAMPS, (SP)-cAMPN(CH3)2, and RP-cAMPN(CH3)2. We have investigated the agonistic and antagonistic activities of these compounds in four cAMP-dependent reactions: activation of the cellular slime mold Dictyostelium discoideum via its cell surface cAMP receptor, and phosphorylation by cAMP-dependent protein kinases type I, type II (both mammalian enzymes), and type D (derived from D. discoideum). The results show that 1) the compounds (SP)-cAMPS and (SP)-cAMPN(CH3)2 are (mostly full) agonists for the four proteins. Half-maximal activation is at micromolar concentrations (0.8-7 microM). 2) (RP)-cAMPS is a full antagonist for the cell surface receptor and protein kinases type I and II, with apparent inhibition constants between 0.8 and 8 microM. This compound is a partial agonist for protein kinase type D, where it induces maximally 50% activation of the enzyme if compared with cAMP. 3) (RP)-cAMPN(CH3)2 is a full antagonist for the cell surface receptor, and for protein kinase type II. This compound is a partial agonist for protein kinase type I (at least 50% activation if compared with cAMP), and inactive for protein kinase type D. This derivative is at least 25-fold less active as an antagonist than (RP)-cAMPS. 4) The activity of mixtures of different concentrations of the antagonist (RP)-cAMPS with different concentrations of cAMP reveals that the compound is a competitive antagonist of cAMP at micromolar concentrations.

Description

Rp-cAMPS triethylammonium salt is an analog of cAMP which acts as a potent, competitive and cell-permeable antagonist of cAMP-induced activation of cAMP-dependent PKA I and II (Kis of 6.05 µM and 9.75 µM, respectively). Rp-cAMPS triethylammonium salt is resistant to hydrolysis by phosphodiesterases.

Keywords:

cAMPS-Rp, triethylammonium salt,151837-09-1,Natural Products,cAMP, buy cAMPS-Rp, triethylammonium salt , cAMPS-Rp, triethylammonium salt supplier , purchase cAMPS-Rp, triethylammonium salt , cAMPS-Rp, triethylammonium salt cost , cAMPS-Rp, triethylammonium salt manufacturer , order cAMPS-Rp, triethylammonium salt , high purity cAMPS-Rp, triethylammonium salt

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: