| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
Phosphodiesterase type 5 (PDE5); PDE5 (IC50 = 2.28 nM); PDE6 (IC50 = 45.2 nM); PDE1 (IC50 = 566 nM); PDE4 (IC50 = 834 nM); PDE11 (IC50 = 6090 nM)
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| 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].
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| ln Vivo |
The intracavernous pressure/blood pressure ratio (ICP/BP) was elevated at all time points at the 5.0 mg/kg dose, 75, 90, 105, and 2.5 mg/kg by TPN729MA (1.25, 2.5, 5.0 mg/kg; 1 dose). elevated blood pressure to intracavernous pressure ratio at 120 minutes[1]. In male beagle dogs, TPN729MA (5.0 μg/kg; administered intravenously) dramatically raises both intracavernous pressure and the intracavernous pressure/blood pressure ratio[1].
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| 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].
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| 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.
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| 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]
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| Molecular Formula |
C29H40N6O8S
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|---|---|
| Molecular Weight |
632.73
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| CAS # |
1422955-52-9
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| Related CAS # |
TPN729;936951-20-1
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| PubChem CID |
136266251
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
44
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| Complexity |
1010
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CNCJOFPBSNINND-BTJKTKAUSA-N
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| InChi Code |
InChI=1S/C25H36N6O4S.C4H4O4/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;5-3(6)1-2-4(7)8/h10-11,17H,5-9,12-16H2,1-4H3,(H,26,27,32);1-2H,(H,5,6)(H,7,8)/b;2-1-
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| Chemical Name |
(Z)-but-2-enedioic acid;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
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| Synonyms |
TPN-729 maleate; TPN729 maleate
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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) |
DMSO: 25 mg/mL (39.51 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5805 mL | 7.9023 mL | 15.8045 mL | |
| 5 mM | 0.3161 mL | 1.5805 mL | 3.1609 mL | |
| 10 mM | 0.1580 mL | 0.7902 mL | 1.5805 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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