| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
Taprenepag (formerly known as CP-544326) is a potent and selective agonist of EP2 (prostaglandin EP receptor 2) with IC50 of 10 nM and EC50 of 2.8 nM. The compound, when dosed as the isopropyl ester prodrug PF-04217329, significantly increased both its ocular bioavailability and corneal permeability. In a clinical study involving patients with primary open angle glaucoma, PF-04217329 (Taprenepag isopropyl), a prodrug of CP-544326 (active acid metabolite), a potent and selective EP(2) receptor agonist, was successfully evaluated for its ocular hypotensive activity. In preclinical species, topical ocular dosing of PF-04217329 resulted in an elevation of cAMP in aqueous humor/iris-ciliary body, indicating in vivo activation of EP(2) target receptors. The treatment was well tolerated. CP-544326 was exposed to the eyes at doses higher than the EC(50) for the EP(2) receptor when PF-04217329 was applied topically. After administering PF-04217329 once daily, normotensive Dutch-belted rabbits, normotensive dogs, and laser-induced ocular hypertensive cynomolgus monkeys showed reductions in IOP of between 30 and 50% in single-day studies, and between 20 and 40% in multiple-day studies when compared to eyes that were dosed with a vehicle. One topical dose resulted in an IOP reduction that lasted for six to twenty-four hours straight. Finally, preclinical data collected thus far seem to favor PF-04217329's clinical development as a novel glaucoma treatment drug.
| Targets |
human EP2 ( IC50 = 10 nM ); rat EP2 ( IC50 = 15 nM )
The therapeutic target is the Prostaglandin E EP2 Receptor (Receptors, Prostaglandin E, EP2 Subtype). CP-544326 is a potent and selective agonist of this receptor, with an IC₅₀ value of 10 nM and an EC₅₀ value of 2.8 nM against the EP₂ receptor[1] |
|---|---|
| ln Vitro |
In vitro activity:
Taprenepag (CP-544326) (0.01-1000 nM) raises cAMP levels in HEK293 cells expressing human EP2 (EC50=2.8 nM). 1. Receptor agonistic activity: CP-544326 exhibits potent agonistic activity on the Prostaglandin E EP2 Receptor, with an IC₅₀ of 10 nM and an EC₅₀ of 2.8 nM in in vitro assays, demonstrating high affinity and agonistic activity for this receptor[1] 2. Physicochemical and absorption properties: CP-544326 itself has poor corneal permeability and low ocular bioavailability. When administered as the isopropyl ester prodrug PF-04217329 (Taprenepag isopropyl), its corneal permeability and ocular bioavailability are significantly increased[1] |
| ln Vivo |
1. Target activation effect: After topical ocular administration of the prodrug PF-04217329, it can be converted into CP-544326 in vivo, and the level of cyclic adenosine monophosphate (cAMP) in the aqueous humor/iris-ciliary body is elevated, indicating that CP-544326 successfully activates the EP₂ target receptor in vivo[1] 2. Ocular exposure level: After topical ocular administration of PF-04217329, the exposure concentration of CP-544326 in ocular tissues is higher than its EC₅₀ value (2.8 nM) for the EP₂ receptor, meeting the concentration requirement for exerting pharmacological effects[1] 3. Intraocular pressure (IOP)-lowering effect (single-day studies): In normotensive Dutch-belted rabbits, normotensive dogs, and laser-induced ocular hypertensive cynomolgus monkeys (preclinical glaucoma models), single daily topical ocular administration of PF-04217329 (which is converted to CP-544326 to exert effects) reduced IOP by 30%-50%, and the IOP-lowering effect after a single dose persisted from 6 hours to 24 hours post-administration[1] 4. Intraocular pressure (IOP)-lowering effect (multiple-day studies): In multiple-day dosing studies, single daily topical ocular administration of PF-04217329 (converted to CP-544326 to exert effects) reduced IOP by 20%-40% compared with vehicle-dosed eyes[1] |
| 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).
|
| Animal Protocol |
1. Experimental animals and models: The experimental animals included normotensive Dutch-belted rabbits, normotensive dogs, and laser-induced ocular hypertensive cynomolgus monkeys (preclinical models of glaucoma); the experimental groups were divided into the treatment group (topical ocular administration of PF-04217329) and the control group (topical ocular administration of vehicle)[1] 2. Administration route and frequency: Topical ocular administration was adopted with a frequency of once daily; the drug was administered in the form of the isopropyl ester prodrug PF-04217329, which was converted into the active form CP-544326 in vivo after topical ocular delivery[1] 3. Observation indicators and duration: In single-day studies, changes in IOP were observed from 6 hours to 24 hours after administration; in multiple-day studies, the magnitude of IOP reduction was continuously observed. Meanwhile, the level of cAMP in the aqueous humor/iris-ciliary body was detected to evaluate EP₂ receptor activation[1] |
| ADME/Pharmacokinetics |
1. Absorption and bioavailability: CP-544326 has poor corneal permeability and low ocular bioavailability; when applied topically to the eye in the form of isopropyl ester prodrug PF-04217329, the corneal permeability and ocular bioavailability of CP-544326 are significantly improved, and its exposure concentration in ocular tissue can be higher than its EC₅₀ value for EP₂ receptor [1] 2. Metabolic transformation: PF-04217329, as an isopropyl ester prodrug of CP-544326, can be metabolized in vivo into the active form CP-544326 after topical ocular administration, thereby exerting its pharmacological effects [1]
|
| Toxicity/Toxicokinetics |
1. Tolerability: Topical ocular administration (PF-04217329, converted to CP-544326) showed good tolerability in preclinical experimental animals, with no significant ocular or systemic toxicity, hepatotoxicity, nephrotoxicity, drug interactions, or plasma protein binding reported [1]
|
| References | |
| Additional Infomation |
Taprenepag has been used in clinical trials to study the treatment of intraocular hypertension and open-angle glaucoma.
See also: Taprenepag Isopropyl (note moved to). 1. Drug association: CP-544326 is the active acidic metabolite of PF-04217329 (Taprenepag Isopropyl), which is an isopropyl ester prodrug of CP-544326. This prodrug was designed to improve corneal permeability and ocular bioavailability of CP-544326 [1]. 2. Development background and indications: Controlling intraocular pressure is crucial for protecting visual function in patients with glaucoma. Prostaglandin FP analogues are the mainstream drugs for treating glaucoma, while EP₂ receptor agonists are a new research and development direction; CP-544326 (in the form of the previous drug PF-04217329) has been evaluated for its intraocular pressure-lowering activity in clinical studies of patients with primary open-angle glaucoma, and preclinical data support its clinical development as a novel glaucoma treatment drug [1] 3. Mechanism of action: CP-544326 exerts its pharmacological effect of lowering intraocular pressure by activating prostaglandin E EP₂ receptors, resulting in an increase in cAMP levels in the aqueous humor/iris ciliary body [1] |
| Molecular Formula |
C24H22N4O5S
|
|---|---|
| Molecular Weight |
478.52028
|
| Exact Mass |
478.131
|
| Elemental Analysis |
C, 60.24; H, 4.63; N, 11.71; O, 16.72; S, 6.70
|
| CAS # |
752187-80-7
|
| Related CAS # |
Taprenepag isopropyl; 1005549-94-9
|
| PubChem CID |
18376177
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.202
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
34
|
| Complexity |
753
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=S(C1=CN=CC=C1)(N(CC2=CC(OCC(O)=O)=CC=C2)CC3=CC=C(N4C=CC=N4)C=C3)=O
|
| InChi Key |
MFFBXYNKZHTCEY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H22N4O5S/c29-24(30)18-33-22-5-1-4-20(14-22)17-27(34(31,32)23-6-2-11-25-15-23)16-19-7-9-21(10-8-19)28-13-3-12-26-28/h1-15H,16-18H2,(H,29,30)
|
| Chemical Name |
2-[3-[[(4-pyrazol-1-ylphenyl)methyl-pyridin-3-ylsulfonylamino]methyl]phenoxy]acetic acid
|
| Synonyms |
Taprenepag; CP-544326; CP544326; CP544326; PF-0421732 metabolite
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.22 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 (5.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0898 mL | 10.4489 mL | 20.8978 mL | |
| 5 mM | 0.4180 mL | 2.0898 mL | 4.1796 mL | |
| 10 mM | 0.2090 mL | 1.0449 mL | 2.0898 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA