Rp-8-Br-PET-cGMPS (sodium) (Rp-8-Bromo-PET-cGMPS) is an analog of cyclic GMP (cGMP). It is a cell-permeable, competitive and reversible inhibitor of cGMP-dependent protein kinase (cGK) that blocks cGMP activation of cGKI and cGKII (Kis=35 and 30 nM). It has weak inhibitory effects on protein kinase A (Ki=11 μM) and cGMP-induced activation of cyclic nucleotide-gated channels (IC50=25 μM). 1,3 In the absence of cGMP stimulation, Rp-8-Bromo-PET-cGMPS acts as a partial agonist of cGKI (Ki=1 μM). Rp-8-Bromo-PET-cGMPS resists hydrolysis by phosphodiesterase 11.

Physicochemical Properties

Molecular Formula	C18H14BRN5NAO6PS
Molecular Weight	562.27
Exact Mass	560.95
Elemental Analysis	C, 38.45; H, 2.51; Br, 14.21; N, 12.46; Na, 4.09; O, 17.07; P, 5.51; S, 5.70
CAS #	185246-32-6
PubChem CID	23695925
Appearance	Typically exists as solids at room temperature
Melting Point	240-300ºC(lit.)
LogP	2.717
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	2
Heavy Atom Count	34
Complexity	940
Defined Atom Stereocenter Count	4
InChi Key	PNUXBFRWMZKKAJ-IPZAVTHYSA-M
InChi Code	InChI=1S/C18H15BrN5O6PS.Na.H2O/c19-17-21-11-14(24(17)16-12(25)13-10(29-16)7-28-31(27,32)30-13)22-18-20-9(6-23(18)15(11)26)8-4-2-1-3-5-8;;/h1-6,10,12-13,16,25H,7H2,(H,20,22)(H,27,32);;1H2/q;+1;/p-1/t10-,12-,13-,16-,31?;;/m1../s1
Chemical Name	sodium;3-[(4aR,6R,7R,7aS)-7-hydroxy-2-oxido-2-sulfanylidene-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-2-bromo-6-phenyl-5H-imidazo[1,2-a]purin-9-one;hydrate
Synonyms	Rp-8-Bromo-PET-cGMPS; Rp-8-Br-PET-cGMPS; 185246-32-6; sodium;3-[(4aR,6R,7R,7aS)-7-hydroxy-2-oxido-2-sulfanylidene-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-2-bromo-6-phenyl-5H-imidazo[1,2-a]purin-9-one;hydrate; DTXSID00635674; PNUXBFRWMZKKAJ-IPZAVTHYSA-M; Rp-8-Bromo-beta-phenyl-1,N2-ethenoguanosine 3',5'-cyclic monophosphorothioate sodium salt; p-beta-Phenyl-1,N2-etheno-8-bromoguanosine 3',5'-cyclic monophosphorothioate sodium salt; Sodium (4aR,6R,7R,7aS)-6-(2-bromo-9-oxo-6-phenyl-5,9-dihydro-3H-imidazo[1,2-a]purin-3-yl)-7-hydroxy-2-sulfanylidenetetrahydro-2H,4H-2lambda~5~-furo[3,2-d][1,3,2]dioxaphosphinin-2-olate--water (1/1/1)
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	cGMP-dependent protein kinases (cGKs)
References	[1]. Activation of PDE10 and PDE11 phosphodiesterases. J. Biol. Chem. 287(2), 1210-1219 (2012).
Additional Infomation	The most recently identified cyclic nucleotide phosphodiesterases, PDE10 and PDE11, contain a tandem of so-called GAF domains in their N-terminal regulatory regions. In PDE2 and PDE5, the GAF domains mediate cGMP stimulation; however, their function in PDE10 and PDE11 remains controversial. Although the GAF domains of PDE10 mediate cAMP-induced stimulation of chimeric adenylyl cyclases, cAMP binding did not stimulate the PDE10 holoenzyme. Comparable data about cGMP and the PDE11 GAF domains exist. Here, we identified synthetic ligands for the GAF domains of PDE10 and PDE11 to reduce interference of the GAF ligand with the catalytic reaction of PDE. With these ligands, GAF-mediated stimulation of the PDE10 and PDE11 holoenzymes is demonstrated for the first time. Furthermore, PDE10 is shown to be activated by cAMP, which paradoxically results in potent competitive inhibition of cGMP turnover by cAMP. PDE11, albeit susceptible to GAF-dependent stimulation, is not activated by the native cyclic nucleotides cAMP and cGMP. In summary, PDE11 can be stimulated by GAF domain ligands, but its native ligand remains to be identified, and PDE10 is the only PDE activated by cAMP. [1]

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7785 mL	8.8925 mL	17.7850 mL
	5 mM	0.3557 mL	1.7785 mL	3.5570 mL
	10 mM	0.1779 mL	0.8893 mL	1.7785 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.