PF04418948
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MedKoo CAT#: 522468

CAS#: 1078166-57-0

Description: 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

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PF04418948
CAS# 1078166-57-0
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522468
Name: PF04418948
CAS#: 1078166-57-0
Chemical Formula: C23H20FNO5
Exact Mass: 409.13
Molecular Weight: 409.410
Elemental Analysis: C, 67.48; H, 4.92; F, 4.64; N, 3.42; O, 19.54

Price and Availability

Size Price Availability Quantity
10mg USD 110 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to ship
500mg USD 2850 Ready to ship
1g USD 4250 2 Weeks
2g USD 6850 2 Weeks
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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:

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 48.90

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.

Recalculate based on batch purity %
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: 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.
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.

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1: Domingo-Gonzalez R, Martínez-Colón GJ, Smith AJ, Smith CK, Ballinger MN, Xia M, Murray S, Kaplan MJ, Yanik GA, Moore BB. Prostaglandin E(2) Inhibits Neutrophil Extracellular Trap Formation Post-stem Cell Transplant. Am J Respir Crit Care Med. 2015 Sep 29. [Epub ahead of print] PubMed PMID: 26417909.

2: Säfholm J, Manson ML, Bood J, Delin I, Orre AC, Bergman P, Al-Ameri M, Dahlén SE, Adner M. Prostaglandin E(2) inhibits mast cell-dependent bronchoconstriction in human small airways through the E prostanoid subtype 2 receptor. J Allergy Clin Immunol. 2015 May 9. pii: S0091-6749(15)00489-3. doi: 10.1016/j.jaci.2015.04.002. [Epub ahead of print] PubMed PMID: 25962903.

3: Martinez-Cutillas M, Mañé N, Gallego D, Jimenez M, Martin MT. EP2 and EP4 receptors mediate PGE2 induced relaxation in murine colonic circular muscle: pharmacological characterization. Pharmacol Res. 2014 Dec;90:76-86. doi: 10.1016/j.phrs.2014.10.001. Epub 2014 Oct 20. PubMed PMID: 25461458.

4: Jiao HY, Kim DH, Ki JS, Ryu KH, Choi S, Jun JY. Effects of lubiprostone on pacemaker activity of interstitial cells of cajal from the mouse colon. Korean J Physiol Pharmacol. 2014 Aug;18(4):341-6. doi: 10.4196/kjpp.2014.18.4.341. Epub 2014 Aug 13. PubMed PMID: 25177167; PubMed Central PMCID: PMC4146637.

5: 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. PubMed PMID: 25003710; PubMed Central PMCID: PMC4164591.

6: Shimizu T, Tanaka K, Nakamura K, Taniuchi K, Yawata T, Higashi Y, Ueba T, Dimitriadis F, Shimizu S, Yokotani K, Saito M. Possible involvement of brain prostaglandin E2 and prostanoid EP3 receptors in prostaglandin E2 glycerol ester-induced activation of central sympathetic outflow in the rat. Neuropharmacology. 2014 Jul;82:19-27. doi: 10.1016/j.neuropharm.2014.03.005. Epub 2014 Mar 19. PubMed PMID: 24657150.

7: Cheah EY, Burcham PC, Mann TS, Henry PJ. Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism. Biochem Pharmacol. 2014 May 1;89(1):148-56. doi: 10.1016/j.bcp.2014.02.009. Epub 2014 Feb 19. PubMed PMID: 24561178.

8: Kach J, Sandbo N, La J, Denner D, Reed EB, Akimova O, Koltsova S, Orlov SN, Dulin NO. Antifibrotic effects of noscapine through activation of prostaglandin E2 receptors and protein kinase A. J Biol Chem. 2014 Mar 14;289(11):7505-13. doi: 10.1074/jbc.M113.546812. Epub 2014 Feb 3. PubMed PMID: 24492608; PubMed Central PMCID: PMC3953264.

9: Säfholm J, Dahlén SE, Adner M. Antagonising EP1 and EP2 receptors reveal that the TP receptor mediates a component of antigen-induced contraction of the guinea pig trachea. Eur J Pharmacol. 2013 Oct 15;718(1-3):277-82. doi: 10.1016/j.ejphar.2013.08.021. Epub 2013 Sep 5. PubMed PMID: 24012781.

10: Kay LJ, Gilbert M, Pullen N, Skerratt S, Farrington J, Seward EP, Peachell PT. Characterization of the EP receptor subtype that mediates the inhibitory effects of prostaglandin E2 on IgE-dependent secretion from human lung mast cells. Clin Exp Allergy. 2013 Jul;43(7):741-51. doi: 10.1111/cea.12142. PubMed PMID: 23786281.

11: Säfholm J, Dahlén SE, Delin I, Maxey K, Stark K, Cardell LO, Adner M. PGE2 maintains the tone of the guinea pig trachea through a balance between activation of contractile EP1 receptors and relaxant EP2 receptors. Br J Pharmacol. 2013 Feb;168(4):794-806. doi: 10.1111/j.1476-5381.2012.02189.x. PubMed PMID: 22934927; PubMed Central PMCID: PMC3631371.

12: Birrell MA, Maher SA, Buckley J, Dale N, Bonvini S, Raemdonck K, Pullen N, Giembycz MA, Belvisi MG. Selectivity profiling of the novel EP2 receptor antagonist, PF-04418948, in functional bioassay systems: atypical affinity at the guinea pig EP2 receptor. Br J Pharmacol. 2013 Jan;168(1):129-38. doi: 10.1111/j.1476-5381.2012.02088.x. PubMed PMID: 22747912; PubMed Central PMCID: PMC3570009.

13: 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.1476-5381.2011.01495.x. Erratum in: Br J Pharmacol. 2012 Jun;166(3):1192. Dosage error in article text. PubMed PMID: 21595651; PubMed Central PMCID: PMC3246710.

14: Birrell MA, Nials AT. At last, a truly selective EP₂ receptor antagonist. Br J Pharmacol. 2011 Dec;164(7):1845-6. doi: 10.1111/j.1476-5381.2011.01494.x. PubMed PMID: 21595650; PubMed Central PMCID: PMC3246709.