| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
PDE5 2.28 nM (IC50) PDE6 45.2 nM (IC50) PDE1 566 nM (IC50) PDE4 834 nM (IC50) PDE11 6090 nM (IC50)
|
|---|---|
| ln Vitro |
The IC50 of TPN729MA, sildenafil, and tadalafil for PDE5 was 2.28, 5.22, and 2.35 nM, respectively. TPN729MA showed 248, 366, 20, and 2671-fold selectivity against PDE1, PDE4, PDE6, and PDE11, respectively. TPN729MA showed excellent selectivity against PDE2, 3, 7, 8, 9, and 10 (>10,000-fold)[1].
|
| ln Vivo |
Intracavernous pressure/blood pressure ratio (ICP/BP) was enhanced at all time points at the 5.0 mg/kg dose and at 75, 90, 105, and 120 minutes at the 2.5 mg/kg dose minutes by TPN729 (1.25, 2.5, 5.0 mg/kg; 1 dose)[1]. In male beagle dogs, TPN729 (5.0 μg/kg; administered intravenously) dramatically raises both intracavernous pressure and the intracavernous pressure/blood pressure ratio[1].
|
| Enzyme Assay |
TPN729MA is a newly developed phosphodiesterase type 5 inhibitor (PDE5i) for the treatment of erectile dysfunction, which offers potential for greater selectivity and longer duration of action than PDE5i in current clinical use. In this study, researchers investigated the in vitro inhibitory potency and selectivity of TPN729MA on PDE isozymes. Methods: The inhibition of 11 human recombinant PDEs by TPN729MA, sildenafil, and tadalafil were determined using radioimmunoassay[1].
|
| Animal Protocol |
Animal/Disease Models: Male SD (Sprague-Dawley) rats with corpora cavernosa complete exposure[1]
Doses: 1.25, 2.5 and 5.0 mg/kg Route of Administration: Intraduodenal (id) injection; 1.25, 2.5 and 5.0 mg/kg, once Experimental Results: Dose-dependently increased the maximum intracavernous pressure (ICP) and ICP/blood pressure (BP). |
| References |
[1]. Wang Z, et al. The selectivity and potency of the new PDE5 inhibitor TPN729MA. J Sex Med. 2013 Nov;10(11):2790-7.
|
| Additional Infomation |
TPN729MA is a newly developed phosphodiesterase type 5 inhibitor (PDE5i) for the treatment of erectile dysfunction, which offers potential for greater selectivity and longer duration of action than PDE5i in current clinical use. Aim: We investigated the in vitro inhibitory potency and selectivity of TPN729MA on PDE isozymes, and its efficacy in animal models. Methods: The inhibition of 11 human recombinant PDEs by TPN729MA, sildenafil, and tadalafil were determined using radioimmunoassay. The effect of TPN729MA and sildenafil on intracavernous pressure (ICP), blood pressure (BP), and ICP/BP ratio were determined in a rat model of erection induced by electric stimulation and in a dog model of erection induced by sodium nitroprusside injection. Main outcome measures: The main outcome measures were IC50 of TPN729MA, sildenafil, and tadalafil for PDE1-PDE11; maximum ICP; BP and ICP/BP ratio. Results: The IC50 of TPN729MA, sildenafil, and tadalafil for PDE5 was 2.28, 5.22, and 2.35 nM, respectively. TPN729MA showed 248, 366, 20, and 2671-fold selectivity against PDE1, PDE4, PDE6, and PDE11, respectively. TPN729MA showed excellent selectivity against PDE2, 3, 7, 8, 9, and 10 (>10,000-fold). In the rat model of erection, TPN729MA (5.0 and 2.5 mg/kg), but not sildenafil, significantly increased the maximum ICP compared with vehicle. Significantly increased ICP/BP was observed in the TPN729MA (5.0 mg/kg) group at all time points, in the TPN729MA (2.5 mg/kg) group at 75, 90, 105, and 120 minutes time points, and in sildenafil group at 75 and 90 minutes time points compared with vehicle. In the dog model of erection, TPN729MA and sildenafil significantly increased ICP and ICP/BP but showed no significant effect on BP compared with vehicle. Conclusions: TPN729MA is a potent PDE5i with a balanced selectivity profile. TPN729MA shows excellent in vitro and in vivo potency, and a longer effect on erectile function than sildenafil in animal model.[1]
|
| Molecular Formula |
C25H36N6O4S
|
|---|---|
| Molecular Weight |
516.656144142151
|
| Exact Mass |
516.251
|
| CAS # |
936951-20-1
|
| Related CAS # |
TPN729MA;1422955-52-9
|
| PubChem CID |
135771982
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
2.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
36
|
| Complexity |
888
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
AMAMTKNTOCJVCV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H36N6O4S/c1-5-9-20-22-23(30(4)28-20)25(32)27-24(26-22)19-17-18(10-11-21(19)35-16-6-2)36(33,34)29(3)14-15-31-12-7-8-13-31/h10-11,17H,5-9,12-16H2,1-4H3,(H,26,27,32)
|
| Chemical Name |
N-methyl-3-(1-methyl-7-oxo-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide
|
| Synonyms |
TPN729; 936951-20-1; SCHEMBL16171277;
|
| 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)
|
| 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
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 | 1.9355 mL | 9.6775 mL | 19.3551 mL | |
| 5 mM | 0.3871 mL | 1.9355 mL | 3.8710 mL | |
| 10 mM | 0.1936 mL | 0.9678 mL | 1.9355 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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