PF-04475270
PF-04475270 is a prodrug of CP-734432 (HY-119236), as well as an agonist of the EP4 prostaglandin receptor, with IC50 values of 2 nM and 8 nM against human and canine sources, respectively. PF-04475270 is rapidly hydrolyzed into its active metabolite CP-734432 by ocular esterases or corneal homogenate, stimulates cAMP production, and activates cAMP response element-mediated β-lactamase activity in cells expressing EP4. PF-04475270 can be used in research related to glaucoma.
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- No. CAS: 1201925-19-0
- Fòrmula: C26H32F3NO4S
- Peso molecular:511.60
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
Descripciòn
IC50 & Target
[1]|
hEP4 2 nM (IC50) |
dog EP4 8 nM (IC50) |
In Vitro
PF-04475270 crosses cornea tissue more robustly than its active metabolite CP-734432[1].
PF-04475270 (10 μM) is rapidly converted to CP-734432 in rabbit corneal homogenates[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:
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Dosage:0.1 μg; 0.25 μg; 2.5 μg; 5 μg (single dose); 0.5 μg; 1.25 μg (once daily for 4 days)
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Administration:topical; single instillation (for 0.1 μg, 0.25 μg, 2.5 μg, 5 μg); once daily; 4 days (for 0.5 μg, 1.25 μg)
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Result:Achieved mean IOP of 73% of baseline at 24 hours post-first dose, 67% of baseline at 48 hours, 65% of baseline at 72 hours, and 65% of baseline at 96 hours for the 0.5 μg multiple-dose group.
Achieved mean IOP of 81% of baseline at 24 hours post-first dose, 64% of baseline at 48 hours, 61% of baseline at 72 hours, and 58% of baseline at 96 hours for the 1.25 μg multiple-dose group.
Demonstrated progressively greater IOP reduction with repeated daily dosing despite no accumulation of the active metabolite CP-734432 in ocular tissues.
Showed a population-based pharmacokinetic-pharmacodynamic model (model II) with a positive feedback loop captured time-dependent IOP lowering, with key parameters including a SC50 of 0.674 ng/g, a Sₘₐₓ of 0.287, and a kₘₒd of 0.029 h-1.
Chemical Information
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No. CAS 1201925-19-0
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Peso molecular 511.60
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Fòrmula C26H32F3NO4S
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SMILES
FC(F)(F)C1=CC=CC(C[C@H](O)CC[C@@H]2N(C(CC2)=O)CCCC3=CC=C(C(OC(C)C)=O)S3)=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocolo
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Pureza y Documentación
Referencias
[1]. Luu KT, et al. Pharmacokinetic-pharmacodynamic and response sensitization modeling of the intraocular pressure-lowering effect of the EP4 Agonist 5-{3-[(2S)-2-{(3R)-3-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-5-oxopyrrolidin-1-yl]propyl}thiophene-2-carboxylate (PF-04475270). J Pharmacol Exp Ther. 2009;331(2):627-635. [Content Brief]
[2]. Prasanna G, et al. Ocular pharmacokinetics and hypotensive activity of PF-04475270, an EP4 prostaglandin agonist in preclinical models. Exp Eye Res. 2009;89(5):608-617. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PF-04475270 Related Classifications
HY-185643 Related Classifications
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