| 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 |
| Targets |
Phosphodiesterase type 5 (PDE5), specifically the PDE5A1 isoform. TPN171 is a potent inhibitor of human PDE5A1 with an IC50 of 0.62 nM. It exhibits high selectivity for PDE5 over other phosphodiesterase isoforms, including a 32-fold selectivity over PDE6 and selectivity ratios exceeding 16,000 for most other isoforms.
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| ln Vitro |
TPN171 demonstrates potent in vitro inhibitory activity against PDE5 with an IC50 of 0.62 nM. It exhibits good metabolic stability, retaining 91.0% of its presence in human liver microsomes. The compound shows a binding affinity (Kd) of 82.0 nM to the PDE5A1 catalytic domain. In vitro solubility data indicates it is soluble in DMSO at approximately 25 mg/mL (~56.62 mM).
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| ln Vivo |
In animal models, TPN171 has been shown to exert a longer-lasting effect than sildenafil, providing a foundation for once-daily oral administration. Its in vivo efficacy supports its development for the treatment of PAH and ED. TPN171 is a clinical candidate being investigated for its therapeutic potential in these indications.
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| Enzyme Assay |
In vitro enzyme assays for TPN171 typically involve measuring its inhibitory activity against PDE5. The compound is incubated with the enzyme and a suitable substrate, and the rate of cGMP hydrolysis is measured. IC50 values are determined from concentration-response curves. Selectivity against other PDE isoforms is assessed using similar assays with isoform-specific enzymes. Binding affinity (Kd) can be determined using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) with the PDE5A1 catalytic domain.
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| Cell Assay |
In vitro cell-based assays are not the primary method for evaluating PDE5 inhibitors, as the target is an enzyme. However, cell-based functional assays can be performed using cell lines expressing PDE5, such as vascular smooth muscle cells. Cells are treated with TPN171, and the accumulation of cGMP is measured following stimulation of the nitric oxide pathway. The compound's ability to potentiate cGMP accumulation and induce vasodilation can be assessed in these cellular models.
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| Animal Protocol |
In vivo animal studies for TPN171 are typically conducted in rodent models of PAH or ED. For PAH, animals are administered TPN171 orally, and hemodynamic parameters such as pulmonary artery pressure are measured. For ED, the compound's effect on erectile function is assessed in relevant models. Pharmacokinetic parameters are also evaluated in these studies. TPN171 has been shown to have a longer duration of action than sildenafil in animal models.
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| ADME/Pharmacokinetics |
TPN171 is orally bioavailable and exhibits favorable pharmacokinetic properties. In Sprague-Dawley rats and Beagle dogs, key PK parameters such as Tmax, Cmax, AUC, MRT, half-life, clearance, volume of distribution, and oral bioavailability have been characterized. In phase 1 clinical trials, the terminal half-life of TPN171 was found to be 10.9 hours. A phase I study has also been conducted to compare its pharmacokinetics and safety in patients with hepatic impairment versus normal hepatic function.
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| Toxicity/Toxicokinetics |
No specific toxicity data are documented for TPN171 in the provided sources. As a clinical candidate, its safety profile is being evaluated in ongoing clinical trials. A Phase II and a registrational Phase III clinical trial have been conducted in patients with ED. A 10 mg dose of TPN171 demonstrated long-term therapeutic efficacy with a favorable safety profile in treating ED.
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| Additional Infomation |
Simmerafil is being investigated in the clinical trial NCT06301854 (long-term safety of TPN171H tablets for the treatment of erectile dysfunction). It is a phosphodiesterase type 5 (PDE5) inhibitor.
TPN171 is also known as Simenafil. It is a clinical candidate for the treatment of PAH and has been approved in China for ED under the brand name 昂伟达® (Simenafil Hydrochloride). Its development was driven by pharmacokinetics optimization. It is currently being developed in China. TPN171 is for research use only and not for therapeutic use. |
| Molecular Formula |
C24H35N5O3
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|---|---|
| Molecular Weight |
441.566405534744
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| Exact Mass |
441.273
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| CAS # |
1229018-87-4
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| Related CAS # |
1229018-87-4;2258665-03-9 (acetate);2258665-04-0 (mesylate);2258665-07-3 (HCl);
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| PubChem CID |
136197286
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| Appearance |
White to off-white solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
727
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCOC1=C(C=C(C=C1)NC(=O)CN2CCN(CC2)C)C3=NC(=C(C(=O)N3)CC)CC
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| InChi Key |
PIOIVHHIGWTEJQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H35N5O3/c1-5-14-32-21-9-8-17(25-22(30)16-29-12-10-28(4)11-13-29)15-19(21)23-26-20(7-3)18(6-2)24(31)27-23/h8-9,15H,5-7,10-14,16H2,1-4H3,(H,25,30)(H,26,27,31)
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| Chemical Name |
N-[3-(4,5-diethyl-6-oxo-1H-pyrimidin-2-yl)-4-propoxyphenyl]-2-(4-methylpiperazin-1-yl)acetamide
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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 |
| 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 (~56.62 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.26 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.26 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 10.0 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: ≥ 1 mg/mL (2.26 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 | 2.2646 mL | 11.3232 mL | 22.6465 mL | |
| 5 mM | 0.4529 mL | 2.2646 mL | 4.5293 mL | |
| 10 mM | 0.2265 mL | 1.1323 mL | 2.2646 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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