CYCLIC NUCLEOTIDES

CYCLIC-AMP AND -GMP ASSAY KITS

The BIOMOL EIA cyclic-AMP and -GMP kits offer a convenient, sensitive and accurate method to quantify cyclic-AMP and -GMP in a variety of samples. The kits are stable at 4°C and assays are completed in 3-4 hours! The BIOMOL EIA cAMP and cGMP kits are a competitive immunoassay that utilizes alkaline phosphatase and pNPP for detection. After a simultaneous incubation of reagents and samples at room temperature, excess reagents are washed away and the substrate is added. A yellow color is generated and the absorbance is measured on a microplate reader at 405 nm. The absorption is inversely proportional to the concentration of cAMP or cGMP in standards or samples. The Format A Kits allow the direct measurement of cAMP or cGMP in cell and tissue samples which have been treated with 0.1M HCl, 80% ethanol, or 5% TCA to inhibit phosphodiesterase activity. The Format B Kits allow measurement of cAMP or cGMP in dried samples, tissue culture media, enzyme assay buffers, or directly from urine.

AK-200
Cyclic AMP Enzyme Immunoassay Kit, Format A
The cAMP concentrations are quantified directly in cell and tissue samples which have been treated with 0.1M HCl, 80% ethanol, or 5% TCA to inhibit phosphodiesterase activity. There is no requirement for solvent evaporation. Sensitivity is increased 10-fold by acetylation (reagents included). Sensitivity: <0.008 pmol/well (acetylated); Range: 5,000 - 0.5 pmol/ml non-acetylated; 500 - 0.05 pmol/ml (acetylated). Storage: 4°C.
1 kit (96 well)
5 kits

AK-250
Cyclic AMP Enzyme Immunoassay Kit, Format B
The cAMP concentrations are quantified in dried samples, or directly from tissue culture media, enzyme assay buffers, and from urine. Sensitivity is increased 10-fold by acetylation (reagents included). Sensitivity: <0.004 pmol/well (acetylated); Range: 5,000 - 0.5 pmol/ml non-acetylated; 500 - 0.05 pmol/ml (acetylated). Storage: 4°C.
1 kit (96 well)
5 kits

AK-300
Cyclic GMP Enzyme Immunoassay Kit, Format A
The cGMP concentrations are quantified directly in cell and tissue samples which have been treated with 0.1M HCl, 80% ethanol, or 5% TCA to inhibit phosphodiesterase activity. There is no requirement for solvent evaporation. Sensitivity is increased 10-fold by acetylation (reagents included). Sensitivity: <0.01 pmol/well (acetylated); Range: 500 - 0.8 pmol/ml non-acetylated; 100 - 0.2 pmol/ml (acetylated). Storage: 4°C
1 kit (96 well)
5 kits

AK-350
Cyclic GMP Enzyme Immunoassay Kit, Format B
The cGMP concentrations are quantified in dried samples, or directly from tissue culture media, enzyme assay buffers, and from urine. Sensitivity is increased 10-fold by acetylation (reagents included). Sensitivity: <0.01 pmol/well (acetylated); Range: 500 - 0.8 pmol/ml non-acetylated; 100 - 0.2 pmol/ml (acetylated). Storage: 4°C
1 kit (96 well)
5 kits


CYCLIC AMP

CYCLIC AMP ANALOGS

CN-115
8-Bromo-cAMP
8-Bromoadenosine-3',5'-cyclic monophosphate, sodium salt
98%, MW=430.1 [76939-46-3] Storage: -20°C
A cell permeable cAMP analog which is more resistant to phosphodiesterases than cAMP and which preferentially activates cAMP-dependent protein kinase^1,2,3.
10 mg
50 mg

CN-135
Rp-cAMPS
Rp-Adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPS)
98%, MW=446.5 [73208-40-9] Storage: -20°C
Rp-cAMPS is a potent and specific competitive inhibitor of the activation of cAMP dependent protein kinases by cAMP⁴ (IC₅₀=4.9 µM)⁵. Its cell permeability and complete resistance to cyclic nucleotide phosphodiesterases⁶ make it a unique tool for studying cAMP-dependent signalling.
1 mg
5 x 1 mg

CN-136
Sp-cAMPS
Sp-Adenosine-3',5'-cyclic monophosphorothioate (Sp-cAMPS)
98%, MW=446.5 [71774-13-5] Storage: -20°C
Sp-cAMPS is a potent and specific activator of cAMP dependent protein kinases⁷ . Its cell permeability and complete resistance to cyclic nucleotide phosphodiesterases⁶ make it a unique tool for studying cAMP-dependent signalling. Concentration for half-maximal activation is 1.8 µM³.
1 mg
5 x 1 mg

CN-130
8-CPT cAMP
8-(4-Chlorophenylthio)-adenosine-3',5'-cyclic monophosphate, sodium salt
96%, MW=493.8 [93882-12-3] Storage: -20°C
A cell permeable cAMP analog which activates cAMP- and cGMP-dependent protein kinase³.
20 mg
100 mg

CN-125
Dibutyryl-cAMP
N⁶,2'-O-Dibutyryladenosine-3',5'-cyclic monophosphate, sodium salt monohydrate
96%, MW=509.4 [16980-89-5] Storage: -20°C
A cell permeable cAMP analog which preferentially activates cAMP-dependent protein kinase^1,2.
20 mg
100 mg

CN-120
Sp-5,6-DCl-cBiMPS
Sp-5,6-dichloro-1-b-D-ribofuranosylbenzimidazole-3',5'-monophosphorothioate
A new cAMP analog which is a potent and specific activator of cAMP-dependent protein kinase. It is cell permeable and is not significantly hydrolyzed by type I, II or III phosphodiesterases. It may be used to distinguish the cAMP- versus the cGMP-mediated signal transduction pathways³.
1 mg
5 x 1 mg


ADENYLATE CYCLASE ACTIVATORS AND INHIBITORS

CN-150
Adenylate cyclase toxin (AC toxin)
90%, MW=177 kDa, Storage: 4°C
AC toxin inserts itself into the membrane of target cells and delivers its adenylate cyclase enzymatic domain to the cell interior^8,9 Its adenylate cyclase activity is then stimulated by endogenous Ca²⁺ and calmodulin. The resulting increase in cAMP concentration can easily reach supraphysiological levels¹⁰. AC toxin is a unique tool for increasing cAMP levels in mammalian cells.
50 µg


CN-110
2',5'-Dideoxyadenosine
98%, MW=235.2 [6698-26-6] Storage: 0°C
A useful, cell permeable inhibitor of adenylate cyclase (ID₅₀=250 µM)¹¹.
5 mg
25 mg

CN-100
Forskolin
99%, MW=410.5 [66575-29-9] Storage: -20°C
Forskolin, a diterpenoid isolated from Coleus forskohlii, interacts directly with the catalytic subunit of adenylate cyclase, activating the enzyme and raising intracellular levels of cAMP^12,13. It is cell permeable and active in vivo producing positive inotropic, platelet anti-aggregatory and anti-hypertensive effects¹⁴.
10 mg
5 x 10 mg
100 mg
NEW PACKAGE SIZE

CN-105
L-858051
7-Deacetyl-7b-(g-N-methylpiperazino)-butyrylforskolin?HCl
99%, MW=627.0, Storage: 0°C
A water soluble forskolin derivative, retaining adenylate cyclase stimulatory activity (EC₅₀=10 µM)¹⁵.
5 mg
5 x 5 mg

CN-145
MDL-12,330A HCl
98%, MW=377.0 [40297-09-4] Storage: -20°C
Adenylate cyclase inhibitor, IC₅₀=250µM¹⁶.
5 mg
25 mg

CN-140
SQ 22536
99%, MW=205.2 [17318-31-9] Storage: 0°C
SQ 22536 is a cell permeable adenylate cyclase inhibitor. It inhibits cAMP production induced by prostaglandin E₁ in platelet lysates (IC₅₀=82 µM) and in intact platelets (IC₅₀=1 µM). It has been successfully employed as a probe for the involvement of adenylate cyclase in a variety of receptor systems including those for prostaglandins^17,18 and neurotransmitters^19,20.
5 mg
25 mg


CYCLIC GMP

CYCLIC GMP ANALOGS

CN-206
Rp-8-pCPT-cGMPS
98%, MW=525.9 [153660-04-9] Storage: -20°C
A cell permeable cGMP antagonist (K_i=0.5 µM) which is resistant to hydrolysis by cyclic nucleotide phosphodiesterases²¹.
1 mg

CN-207
Sp-8-pCPT-cGMPS
98%, MW=525.9, Storage: -20°C
A cell permeable cGMP mimetic which is resistant to hydrolysis by cyclic nucleotide phosphodiesterases. Stimulates both cGMP- and cAMP-dependent protein kinases with similar potency²².
1 mg

CN-205
8-Bromo-cGMP
8-Bromoguanosine-3',5'-cyclic monophosphate, sodium salt
96%, MW=446.1 [51116-01-9] Storage: -20°C
A cell permeable cGMP analog which is more resistant to phosphodiesterases than cGMP and which preferentially activates cGMP-dependent protein kinase^1,23,24. It inhibits thrombin stimulated arachidonic acid release in human platelets²⁵.
10 mg
50 mg

CN-216
Rp-8-Br-cGMPS
Rp-8-Bromoguanosine-3',5'-cyclic monophosphorothioate, sodium salt
98%, MW=462.2 [150418-07-8] Storage: -20°C
Cell permeable, phosphodiesterase-resistant cGMP antagonist^26,27,28.
0.5 mg

CN-217
Sp-8-Br-cGMPS
Sp-8-Bromoguanosine-3',5'-cyclic monophosphorothioate, sodium salt
98%, MW=462.2 [153660-03-8] Storage: -20°C
Cell permeable, phosphodiesterase-resistant cGMP agonist. This analog activates PKA and PKG with similar potency²⁹.
0.5 mg

CN-215
Dibutyryl-cGMP
N2,2'-O-Dibutyrylguanosine-3',5'-cyclic monophosphate, sodium salt
96%, MW=507.4 [51116-00-8] Storage: -20°C
A cell permeable cGMP analog which preferentially activates cGMP-dependent protein kinase1,23,24. It inhibits thrombin stimulated arachidonic acid release in human platelets²⁵.
10 mg
50 mg


GUANYLATE CYCLASE ACTIVATORS AND INHIBITORS

HP-012
12-HPETE
12-HPETE (12-hydroperoxy-5,8,10,14-eicosatetraenoic acid) is a potent inhibitor of platelet activation which is due to activation of soluble guanylate cyclase. 12-HPETE produces a rapid and dose-dependent activation (100% at 5 µM) of soluble guanylate cyclase in intact human platelets³⁰.

CN-221
ODQ
1H-[1,2,4]-Oxadiazolo-[4,3-a]-quinoxalin-1-one
98%, MW=187.2, Storage: -20°C
ODQ is a potent and selective, direct-acting inhibitor of guanylate cyclase (IC₅₀=20 nM)³¹. In cerebellar slices ODQ reversibly inhibited cGMP generation in response to endogenous NO or exogenously added NO-donors. ODQ does not inhibit NO-mediated macrophage toxicity (a phenomenon unrelated to cGMP) and does not inhibit particulate guanylyl cyclase or adenylyl cyclase³². ODQ is a new, unique and selective tool to elucidate the physiological importance of the NO-cGMP pathway^33,34,35.
10 mg
50 mg

CN-200
LY 83583
6-Anilino-5,8-quinolinedione
97%, MW=250.3 [91300-60-6] Storage: 0°C
LY 83583 inhibits nitric oxide-induced activation of soluble guanylate cyclase (IC₅₀=2 µM) in a dose-dependent and reversible manner³⁶. It blocks antigen-induced leukotriene release³⁷ and reduces platelet-endothelial cell adhesion³⁶.

CN-220
Guanylin
98%, MW=1514.5, Storage: -20°C
Guanylin is an endogenous ligand and activator of guanylyl cyclase C (GC-C)³⁸. GC-C (also known as intestinal guanylate cyclase) possesses an extracellular ligand binding domain, a transmembrane domain, an intracellular protein kinase-like region and a cyclase catalytic domain³⁹. GC-C is expressed in various mammalian tissues including intestine, adrenal gland, airway epithelial cells, brain, and olfactory and tracheal mucosa⁴⁰.
100 µg
500 µg

CN-230
Protoporphyrin-9
97%, MW=562.7 [553-12-8] Storage: -20°C
Protoporphyrin-9 binds to and activates soluble guanylate cyclase⁴¹. A useful reagent in cases where the use of NO or NO donors is undesirable.
200 mg
1 g

For additional guanylate cyclase activators, see Nitric Oxide Reagents

PHOSPHODIESTERASE INHIBITORS

The inactivation of cAMP and cGMP is catalyzed by a large number of different cyclic nucleotide phosphodiesterases (PDEs)^42,43. Recent reports have revealed the existence of at least five different isozyme families and more than twenty different enzymes⁴⁴. Many isozymes are differentially expressed in different cell types offering opportunities for the development of novel therapeutics. A number of selective inhibitors have been described (See Table 7 below and references 44and 45).


TABLE 7. SELECTIVITY OF PHOSPHODIESTERASE INHIBITORS

PD-125
Cilostamide (OPC 3689)
98%, MW=342.2 [68550-75-4] Storage: RT
Phosphodiesterase PDE III inhibitor, IC₅₀=5 nM⁴⁶.
5 mg
25 mg

EI-127
Dipyridamole
99%, MW=504.6 [58-32-2] Storage: -20°C
Selective inhibitor of cGMP phosphodiesterase (PDE V, IC₅₀=0.9 µM)⁴⁷. Inhibits nucleoside transport into mammalian cells⁴⁸. A widely used antithrombotic, coronary vasodilator.
1 g
5 g

PD-129
EHNA
erythro-9-(2-Hydroxy-3-nonyl)adenine·HCl
98%, MW=313.8 [51350-19-7] Storage: RT
Phosphodiesterase PDE II inhibitor, IC₅₀=0.8 µM^49,50. Also inhibits adenosine deaminase, K_i=4 nM⁵¹.
10 mg
50 mg

PD-130
Etazolate (SQ 20009)
98%, MW=324.8 [51022-77-6] Storage: RT
Selective inhibitor of cAMP-specific phosphodiesterase (PDE IV, IC₅₀=2 µM)^52,53.
5 mg
25 mg

PD-140
IBMX
3-Isobutyl-1-methylxanthine
99%, MW=222.2 [28822-58-4] Storage: RT
A nonspecific inhibitor of phosphodiesterases⁵⁴.
200 mg
1 g

PD-150
8-Methoxymethyl-IBMX
8-Methoxymethyl-1-methyl-3-(2-methylpropyl)xanthine
98%, MW=266.3 [78033-08-6] Storage: RT
Selective inhibitor of Ca²⁺-calmodulin-dependent phosphodiesterase (PDE I, IC₅₀=4 µM)^55,56.
10 mg
50 mg

PD-152
Milrinone
1,6-Dihydro-2-methyl-6-oxo-3,4-bipyridine-5-carbonitrile
97%, MW=211.2 [78415-72-2] Storage: 0°C
Selective inhibitor of cGMP-inhibited phosphodiesterase (PDE III, IC₅₀=0.3 µM)⁵⁷.
10 mg
50 mg

PD-155
MY-5445
1-(3-Chlorophenylamino)-4-phenylphthalazine
99%, MW=331.8 [78351-75-4] Storage: RT
Selective inhibitor of cGMP-specific phosphodiesterase (PDE V, IC₅₀=0.6 µM)⁵⁸.
10 mg
50 mg

PD-170
Quazinone (Ro 13-6438)
98%, MW=235.7 [70018-51-8] Storage: RT
Selective inhibitor of cGMP-inhibited phosphodiesterase (PDE III, IC₅₀=0.6 µM)⁵⁹.
10 mg
50 mg

EI-117
Ro 20-1724
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
99%, MW=278.4 [29925-17-5] Storage: RT
Selective inhibitor of cAMP-specific phosphodiesterase (PDE IV, IC₅₀=2 µM)^60,61,62. The use of this agent in a cell culture model of the blood-brain barrier has recently been described⁶³.
100 mg
1 g

PD-175
Rolipram
98%, MW=275.4 [61413-54-5] Storage: RT
Selective inhibitor of cAMP-specific phosphodiesterase (PDE IV, IC₅₀=1 µM)^61,64. A rolipram insensitive PDE IV subtype has recently been described⁶⁵.
10 mg
50 mg

PD-180
Trequinsin (HL 725)
98%, MW=442.0 [78416-81-6] Storage: RT
A selective, ultrapotent inhibitor of cGMP-inhibited phosphodiesterase (PDE III, IC₅₀=0.3 nM)⁶⁶.
10 mg
5 x 10 mg

PD-185
Vinpocetine
98%, MW=350.5 [42971-09-5] Storage: RT
Selective inhibitor of Ca²⁺/calmodulin-dependent phosphodiesterase (PDE I, IC₅₀=20 µM)^56,67.
20 mg
100 mg

PD-190
Zaprinast (M&B 22948)
98%, MW=271.3 [37762-06-4] Storage: RT
Selective inhibitor of cGMP specific phosphodiesterase (PDE V, IC₅₀=0.8 µM)^68,69. Increases cGMP levels in SHR plasma. Reverses nitroglycerin tolerance in vitro⁷¹.
20 mg
100 mg

PD-195
Zardaverine
98%, MW=268.2 [101975-10-4] Storage: RT
Selective, dual inhibitor of PDE III and IV (IC₅₀s=2.5 and 1.1 µM respectively)⁷². Anti-allergic activity⁷².
5 mg
25 mg


PROTEINS

SE-103
Phosphodiesterase (from bovine brain)
3', 5'-cyclic-nucleotide phosphodiesterase
(EC 3.1.4.17) [9040-59-9] Storage: -20°C
Supplied partially purified, lyophilized. Specific activity: 1-5 U/mg protein. One unit will hydrolyze 1 µmol 3',5'-cAMP to 5'-AMP per minute at pH 7.5 and 30°C.
0.25 U
1 U


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