| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
EP2
Taprenepag isopropyl is a prodrug that is converted to its active metabolite CP-544326 (Taprenepag), which targets the prostaglandin EP2 receptor. EP2 is a G protein-coupled receptor that is activated by prostaglandin E2 (PGE2). Activation of EP2 receptor stimulates adenylyl cyclase, increases intracellular cAMP levels, and mediates various physiological effects, including smooth muscle relaxation and reduction of intraocular pressure. |
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| ln Vitro |
Tappenepag isopropyl is a very selective EP2 receptor agonist. When the left eye receives a vehicle dosage, its intraocular pressure (IOP) usually stays within normal limits. In the right (Taprenepag isopropyl-dosed) eye, IOP is reduced in all dose groups. On Days 22 and 29, the IOP in the high-dose group is so low that it is not measurable (<4mm Hg). With Taprenepag isopropyl administration, there are no clinical signs or changes in body weight observed at any dose, and animals in the low-dose group (0.75 mg/day) do not exhibit any ocular findings[1].
In vitro, taprenepag isopropyl is a highly selective EP2 receptor agonist. Its active metabolite CP-544326 is a potent and selective EP2 agonist with an IC50 of 10 nM and an EC50 of 2.8 nM. The compound is used in research related to prostaglandin signaling and ocular pharmacology. Specific cellular assay data, such as EC50 values for cAMP accumulation, are not detailed in the available sources. |
| ln Vivo |
In vivo, taprenepag isopropyl (PF-04217329) is a prodrug of CP-544326 and is used in ocular research. After ocular administration, the prodrug is converted to the active EP2 agonist, causing cAMP elevation and reduction of intraocular pressure (IOP). This makes it a potential therapeutic agent for the treatment of glaucoma. Specific animal model data are not detailed in the available sources beyond its characterization as an IOP-lowering agent. |
| Enzyme Assay |
CP-544326 is a novel, selective and potent EP2 agonist. CP-544326 is at least 270 times more selective for the human EP2 subtype than the other human EP subtypes, 1, 3, and 4, with an IC50 for human EP2 equal to 10 nM (average of two independent experiments; 9 and 11 nM). cAMP levels increased in a dose- and time-dependent manner, yielding an average EC50 of 1.9 nM (1.5 and 2.4 nM; from two independent experiments), according to the cell-based efficacy data using rat EP2-HEP293 cells. The EC50 of 2.8 nM (2.5 and 3.1 nM; from two independent experiments) for CP-544326-mediated cAMP production in human EP2-HEK293 cells was comparable to that of PGE2 (EC50 = 2.6 nM).
The EP2 receptor binding assay for taprenepag isopropyl or its active metabolite CP-544326 involves incubating the compound with membrane preparations from cells expressing the human EP2 receptor and a radiolabeled PGE2 ligand. After incubation, bound and free ligands are separated by filtration, and the radioactivity is counted. The IC50 or Ki for displacement of the radioligand is calculated from the competition curve. Functional agonism is assessed using a cAMP assay in cells expressing EP2. |
| Cell Assay |
To evaluate the cellular activity of taprenepag isopropyl, cells expressing the human EP2 receptor are seeded in 96-well plates and treated with varying concentrations of the compound or its active metabolite CP-544326. Intracellular cAMP levels are measured using a cAMP assay kit. The EC50 for cAMP accumulation is calculated. The compound's selectivity can be assessed by testing against other prostaglandin receptor subtypes (EP1, EP3, EP4, DP, FP, IP, TP).
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| Animal Protocol |
In this study, three-year-old male cynomolgus monkeys weighing between 2.6 and 5.0 kg are employed. For 28 days, animals receive two daily doses of Taprenepag isopropyl (0.75, 12, or 36 mg/day) in the right eye, and an equivalent volume of vehicle (containing BAC, EDTA, boric acid, and cremophor) in the left eye. To monitor recovery over a 28-day period, 2 more monkeys are added to the high-dose group. The evaluation of clinical signs, body weight, ophthalmic examination, pupillary diameter, corneal staining, pachymetry, and noncontact specular microscopy are the main factors that determine the toxicity outcomes. On Days 1, 8, 15, 22, and 29 of the dosing phase, IOP is measured once during the predose phase and prior to dosing. Thereafter, it is measured once every week for the duration of the recovery period[1].
The in vivo efficacy of taprenepag isopropyl is evaluated in animal models of ocular hypertension, such as laser-induced ocular hypertension models in rabbits or monkeys. Intraocular pressure (IOP) is measured using a tonometer before and after administration of the compound. Taprenepag isopropyl is administered topically as eye drops at various concentrations. The reduction in IOP is expressed as the percentage decrease from baseline and compared to vehicle-treated controls. Duration of action is also assessed. |
| ADME/Pharmacokinetics |
Taprenepag isopropyl is a prodrug designed for ocular administration. Its active metabolite CP-544326 is a potent EP2 agonist with an IC50 of 10 nM. Specific pharmacokinetic parameters for the prodrug and its active metabolite (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 520.6 and is soluble in DMSO at 200 mg/mL.
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| Toxicity/Toxicokinetics |
Specific toxicity data for taprenepag isopropyl are not provided in the available sources. As a research compound intended for ocular administration, its safety profile has likely been evaluated in preclinical studies. The compound is intended for research use only and is not approved for human therapeutic applications. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Taprenepag isopropyl is also known as PF-04217329. It is a prodrug of CP-544326 (Taprenepag), which is a potent and selective EP2 receptor agonist with an IC50 of 10 nM and an EC50 of 2.8 nM. It is used in research related to prostaglandin signaling and ocular pharmacology, particularly for the potential treatment of glaucoma.
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| Molecular Formula |
C27H28N4O5S
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| Molecular Weight |
520.60
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| Exact Mass |
520.178
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| Elemental Analysis |
C, 62.29; H, 5.42; N, 10.76; O, 15.37; S, 6.16
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| CAS # |
1005549-94-9
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| Related CAS # |
Taprenepag; 752187-80-7
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| PubChem CID |
23729077
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| Appearance |
White to off-white solid powder
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| LogP |
5.069
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
37
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| Complexity |
812
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=NC=CC=1)(N(CC1C=CC=C(C=1)OCC(=O)OC(C)C)CC1C=CC(=CC=1)N1C=CC=N1)(=O)=O
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| InChi Key |
NVPXUFQLKWKBHK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H28N4O5S/c1-21(2)36-27(32)20-35-25-7-3-6-23(16-25)19-30(37(33,34)26-8-4-13-28-17-26)18-22-9-11-24(12-10-22)31-15-5-14-29-31/h3-17,21H,18-20H2,1-2H3
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| Chemical Name |
propan-2-yl 2-[3-[[(4-pyrazol-1-ylphenyl)methyl-pyridin-3-ylsulfonylamino]methyl]phenoxy]acetate
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (9.60 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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: 5 mg/mL (9.60 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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: ≥ 5 mg/mL (9.60 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 | 1.9209 mL | 9.6043 mL | 19.2086 mL | |
| 5 mM | 0.3842 mL | 1.9209 mL | 3.8417 mL | |
| 10 mM | 0.1921 mL | 0.9604 mL | 1.9209 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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