PF04418948 | CAS#1078166-57-0 | EP2 receptor antagonist

MedKoo Cat#: 522468 | Name: PF04418948

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PF-04418948 is a novel, potent and selective prostaglandin EP2 receptor antagonist. PF-04418948 inhibited prostaglandin E(2)(PGE(2))-induced increase in cAMP in cells expressing EP(2) receptors with a functional K(B) value of 1.8 nM. In human myometrium, PF-04418948 produced a parallel, rightward shift of the butaprost-induced inhibition of the contractions induced by electrical field stimulation with an apparent K(B) of 5.4 nM. In dog bronchiole and mouse trachea, PF-04418948 produced parallel rightward shifts of the PGE(2)-induced relaxation curve with a K(B) of 2.5 nM and an apparent K(B) of 1.3 nM respectively. Reversal of the PGE(2)-induced relaxation in the mouse trachea by PF-04418948 produced an IC(50) value of 2.7 nM.

Chemical Structure

PF04418948

CAS#1078166-57-0

Theoretical Analysis

MedKoo Cat#: 522468

Name: PF04418948

CAS#: 1078166-57-0

Chemical Formula: C23H20FNO5

Exact Mass: 409.1326

Molecular Weight: 409.41

Elemental Analysis: C, 67.48; H, 4.92; F, 4.64; N, 3.42; O, 19.54

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship

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Synonym

PF04418948; PF-04418948; PF 04418948; PF4418948; PF-4418948; PF 4418948.

IUPAC/Chemical Name

1-(4-Fluorobenzoyl)-3-[[(6-methoxy-2-naphthalenyl)oxy]methyl]-3-azetidinecarboxylic acid

InChi Key

LWJGMYMNSNVCEM-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H20FNO5/c1-29-19-8-4-17-11-20(9-5-16(17)10-19)30-14-23(22(27)28)12-25(13-23)21(26)15-2-6-18(24)7-3-15/h2-11H,12-14H2,1H3,(H,27,28)

SMILES Code

O=C(C1(COC2=CC=C3C=C(OC)C=CC3=C2)CN(C(C4=CC=C(C=C4)F)=O)C1)O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#B9B01C16

QC Data

View QC data: current batch, Lot#B9B01C16

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PF-04418948 is a selective prostaglandin EP2 receptor antagonist with an IC50 of 16 nM.

In vitro activity:

In the present study, to clarify the mechanisms underlying PGE2-induced neurotoxicity, generation of intracellular reactive oxygen species (ROS) was focused on and the effects of N-acetylcysteine (NAC), a cell-permeable antioxidant, on PGE2-induced cell death in differentiated NSC-34 cells were examined. DCF analysis showed that the generation of ROS caused by PGE2 at 80 μM was attenuated significantly in the presence of PF-04418948, an EP2-selective antagonist, at 30 μM (Figure 1(b)). In contrast, L-798,106, an EP3-selective antagonist, at 10 μM did not suppress PGE2-induced ROS production (Figure 1(b)). PF-04418948 and L-798,106 did not change ROS formation in differentiated NSC-34 cells. These findings suggest that PGE2 is a lipid mediator with key links to inflammation and oxidative stress. Oxid Med Cell Longev. 2020; 2020: 6101838.Published online 2020 Jan 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201578/

In vivo activity:

This study explored here in the trigeminal ganglion (TG) whether IL-1β upregulated Nav1.7 expression and whether the IL-1β located in the SGCs upregulated Nav1.7 expression in the neurons contributing to TMJ inflammatory hypernociception. Rat TG explants were treated with IL-1β with or without inhibitors, including NS398 for COX-2, PF-04418948 for EP2, and H89 and PKI-(6-22)-amide for protein kinase A (PKA), or with adenylate cyclase agonist forskolin, and used real-time PCR, Western blot, and immunohistofluorescence to determine the expressions or locations of Nav1.7, COX-2, cAMP response element-binding protein Treatment with PF-04418948, an EP2 selective antagonist, completely blocked the IL-1β-induced upregulation of Nav1.7 expression, but not COX-2 expression. This study also showed that the COX-2 inhibitor NS-398 or the EP2 inhibitor PF-04418948 blocked the upregulation of phospho-CREB (P < 0.05; Fig. 3c, d). J Neuroinflammation. 2018; 15: 117.Published online 2018 Apr 20 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910598/

	Solvent	mg/mL	mM
Solubility
	DMSO	20.0	48.90

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 409.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Kosuge Y, Nango H, Kasai H, Yanagi T, Mawatari T, Nishiyama K, Miyagishi H, Ishige K, Ito Y. Generation of Cellular Reactive Oxygen Species by Activation of the EP2 Receptor Contributes to Prostaglandin E2-Induced Cytotoxicity in Motor Neuron-Like NSC-34 Cells. Oxid Med Cell Longev. 2020 Jan 11;2020:6101838. doi: 10.1155/2020/6101838. PMID: 32411331; PMCID: PMC7201578. 2. af Forselles KJ, Root J, Clarke T, Davey D, Aughton K, Dack K, Pullen N. In vitro and in vivo characterization of PF-04418948, a novel, potent and selective prostaglandin EP₂ receptor antagonist. Br J Pharmacol. 2011 Dec;164(7):1847-56. doi: 10.1111/j.14765381.2011.01495.x. Erratum in: Br J Pharmacol. 2012 Jun;166(3):1192. Dosage error in article text. PMID: 21595651; PMCID: PMC3246710. 3. Zhang P, Bi RY, Gan YH. Glial interleukin-1β upregulates neuronal sodium channel 1.7 in trigeminal ganglion contributing to temporomandibular joint inflammatory hypernociception in rats. J Neuroinflammation. 2018 Apr 20;15(1):117. doi: 10.1186/s12974018-1154-0. PMID: 29678208; PMCID: PMC5910598. 4. Stone AJ, Copp SW, Kaufman MP. Role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrated rats. Neuroscience. 2014 Sep 26;277:26-35. doi: 10.1016/j.neuroscience.2014.06.061. Epub 2014 Jul 5. PMID: 25003710; PMCID: PMC4164591.

In vitro protocol:

In vivo protocol:

1. Zhang P, Bi RY, Gan YH. Glial interleukin-1β upregulates neuronal sodium channel 1.7 in trigeminal ganglion contributing to temporomandibular joint inflammatory hypernociception in rats. J Neuroinflammation. 2018 Apr 20;15(1):117. doi: 10.1186/s12974018-1154-0. PMID: 29678208; PMCID: PMC5910598. 2. 2. Stone AJ, Copp SW, Kaufman MP. Role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrated rats. Neuroscience. 2014 Sep 26;277:26-35. doi: 10.1016/j.neuroscience.2014.06.061. Epub 2014 Jul 5. PMID: 25003710; PMCID: PMC4164591.

1: Nazabal A, Mendiguren A, Pineda J. Inhibition of rat locus coeruleus neurons by prostaglandin E2 EP3 receptors: pharmacological characterization ex vivo. Front Pharmacol. 2023 Nov 15;14:1290605. doi: 10.3389/fphar.2023.1290605. PMID: 38035000; PMCID: PMC10684765. 2: Ernst C, Bek T. Differential effects of purines and prostaglandins on hypoxia induced dilatation of porcine retinal vessels at different branching level ex vivo. Exp Eye Res. 2023 Sep;234:109584. doi: 10.1016/j.exer.2023.109584. Epub 2023 Jul 15. PMID: 37460082. 3: Tyler JL, Noble A, Aggarwal VK. Four-Component Strain-Release-Driven Synthesis of Functionalized Azetidines. Angew Chem Int Ed Engl. 2022 Dec 23;61(52):e202214049. doi: 10.1002/anie.202214049. Epub 2022 Nov 27. PMID: 36300572; PMCID: PMC10099845. 4: Mori A, Seki H, Mizukoshi S, Uezono T, Sakamoto K. Role of Prostaglandins in Nitric Oxide-Induced Glial Cell-Mediated Vasodilation in Rat Retina. Biomolecules. 2022 Oct 1;12(10):1403. doi: 10.3390/biom12101403. PMID: 36291611; PMCID: PMC9599243. 5: Boeno CN, Paloschi MV, Lopes JA, Souza Silva MD, Evangelista JR, Dos Reis VP, da S Setúbal S, Soares AM, Zuliani JP. Dynamics of action of a Lys-49 and an Asp-49 PLA2s on inflammasome NLRP3 activation in murine macrophages. Int Immunopharmacol. 2022 Nov;112:109194. doi: 10.1016/j.intimp.2022.109194. Epub 2022 Aug 27. PMID: 36041255. 6: Luu VT, Phan S, Jin ZQ. Dedifferentiation of Human Cardiac Myofibroblasts Is Independent of Activation of COX-2/PGE2 Pathway. Int J Mol Sci. 2022 Mar 11;23(6):3023. doi: 10.3390/ijms23063023. PMID: 35328443; PMCID: PMC8952377. 7: Morgan LM, Martin SL, Mullins ND, Hollywood MA, Thornbury KD, Sergeant GP. Modulation of carbachol-induced Ca2+ oscillations in airway smooth muscle cells by PGE2. Cell Calcium. 2022 May;103:102547. doi: 10.1016/j.ceca.2022.102547. Epub 2022 Feb 2. PMID: 35134593. 8: Nagano T, Tsuda N, Fujimura K, Ikezawa Y, Higashi Y, Kimura SH. Prostaglandin E2 increases the expression of cyclooxygenase-2 in cultured rat microglia. J Neuroimmunol. 2021 Dec 15;361:577724. doi: 10.1016/j.jneuroim.2021.577724. Epub 2021 Sep 23. PMID: 34610503. 9: Sousa FBM, Pacheco G, Oliveira AP, Nicolau LAD, Lopes ALF, Ferreira-Fernandes H, Pinto GR, Medeiros JVR. Mechanism of preservation of the intestinal mucosa architecture and NF-κB/PGE2 reduction by hydrogen sulfide on cholera toxin- induced diarrhea in mice. Life Sci. 2021 Nov 1;284:119869. doi: 10.1016/j.lfs.2021.119869. Epub 2021 Aug 3. PMID: 34358552. 10: Corboz MR, Salvail W, Gagnon S, LaSala D, Laurent CE, Salvail D, Chen KJ, Cipolla D, Perkins WR, Chapman RW. Prostanoid receptor subtypes involved in treprostinil-mediated vasodilation of rat pulmonary arteries and in treprostinil-mediated inhibition of collagen gene expression of human lung fibroblasts. Prostaglandins Other Lipid Mediat. 2021 Feb;152:106486. doi: 10.1016/j.prostaglandins.2020.106486. Epub 2020 Oct 1. PMID: 33011365. 11: Lannoy M, Valluru MK, Chang L, Abdela-Ali F, Peters DJM, Streets AJ, Ong ACM. The positive effect of selective prostaglandin E2 receptor EP2 and EP4 blockade on cystogenesis in vitro is counteracted by increased kidney inflammation in vivo. Kidney Int. 2020 Aug;98(2):404-419. doi: 10.1016/j.kint.2020.02.012. Epub 2020 Mar 6. PMID: 32622526. 12: Kosuge Y, Nango H, Kasai H, Yanagi T, Mawatari T, Nishiyama K, Miyagishi H, Ishige K, Ito Y. Generation of Cellular Reactive Oxygen Species by Activation of the EP2 Receptor Contributes to Prostaglandin E2-Induced Cytotoxicity in Motor Neuron-Like NSC-34 Cells. Oxid Med Cell Longev. 2020 Jan 11;2020:6101838. doi: 10.1155/2020/6101838. PMID: 32411331; PMCID: PMC7201578. 13: Watanabe Y, Imanishi Y, Ozawa H, Sakamoto K, Fujii R, Shigetomi S, Habu N, Otsuka K, Sato Y, Sekimizu M, Ito F, Ikari Y, Saito S, Kameyama K, Ogawa K. Selective EP2 and Cox-2 inhibition suppresses cell migration by reversing epithelial-to-mesenchymal transition and Cox-2 overexpression and E-cadherin downregulation are implicated in neck metastasis of hypopharyngeal cancer. Am J Transl Res. 2020 Mar 15;12(3):1096-1113. PMID: 32269737; PMCID: PMC7137058. 14: Golden J, Illingworth L, Kavarian P, Escobar O, Delaplain P, Isani M, Wang J, Lim J, Bowling J, Bell B, Gayer CP, Grishin A, Ford HR. EP2 Receptor Blockade Attenuates COX-2 Upregulation During Intestinal Inflammation. Shock. 2020 Sep;54(3):394-401. doi: 10.1097/SHK.0000000000001444. PMID: 31490357; PMCID: PMC7051888. 15: Schoos A, Gabriel C, Knab VM, Fux DA. Activation of HIF-1α by δ-Opioid Receptors Induces COX-2 Expression in Breast Cancer Cells and Leads to Paracrine Activation of Vascular Endothelial Cells. J Pharmacol Exp Ther. 2019 Sep;370(3):480-489. doi: 10.1124/jpet.119.257501. Epub 2019 Jul 12. PMID: 31300611. 16: Bradbury P, Rumzhum NN, Ammit AJ. EP2 and EP4 receptor antagonists: Impact on cytokine production and β2 -adrenergic receptor desensitization in human airway smooth muscle. J Cell Physiol. 2019 Jul;234(7):11070-11077. doi: 10.1002/jcp.27938. Epub 2018 Dec 7. PMID: 30536718. 17: Patel JA, Shen L, Hall SM, Benyahia C, Norel X, McAnulty RJ, Moledina S, Silverstein AM, Whittle BJ, Clapp LH. Prostanoid EP₂ Receptors Are Up-Regulated in Human Pulmonary Arterial Hypertension: A Key Anti-Proliferative Target for Treprostinil in Smooth Muscle Cells. Int J Mol Sci. 2018 Aug 12;19(8):2372. doi: 10.3390/ijms19082372. PMID: 30103548; PMCID: PMC6121445. 18: Zhang P, Bi RY, Gan YH. Glial interleukin-1β upregulates neuronal sodium channel 1.7 in trigeminal ganglion contributing to temporomandibular joint inflammatory hypernociception in rats. J Neuroinflammation. 2018 Apr 20;15(1):117. doi: 10.1186/s12974-018-1154-0. PMID: 29678208; PMCID: PMC5910598. 19: Aoki T, Narumiya S. Prostaglandin E2-EP2 signaling as a node of chronic inflammation in the colon tumor microenvironment. Inflamm Regen. 2017 Mar 1;37:4. doi: 10.1186/s41232-017-0036-7. PMID: 29259703; PMCID: PMC5725845. 20: Li H, Chen HY, Liu WX, Jia XX, Zhang JG, Ma CL, Zhang XJ, Yu F, Cong B. Prostaglandin E2 restrains human Treg cell differentiation via E prostanoid receptor 2-protein kinase A signaling. Immunol Lett. 2017 Nov;191:63-72. doi: 10.1016/j.imlet.2017.09.009. Epub 2017 Sep 28. PMID: 28963072.