ONO-AE3-208 | CAS#402473-54-5 | EP4 antagonist

MedKoo Cat#: 406814 | Name: ONO-AE3-208

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Description:

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

ONO-AE3-208 is a potent n EP4 antagonist (Ki = 1.3 nM). ONO-AE3-208 suppresses cell invasion, migration, and metastasis of prostate cancer. The in vitro cell invasion and migration were suppressed by ONO-AE3-208 in a dose-dependent manner without affecting cell proliferation. The in vivo bone metastasis of PC3 was also suppressed by ONO-AE3-208 treatment. EP4 expression levels were correlated with prostate cancer cell invasiveness and EP4 specific antagonist ONO-AE3-208 suppressed cell invasion, migration, and bone metastasis, indicating that it is a potential novel therapeutic modality for the treatment of metastatic prostate cancer.

Chemical Structure

ONO-AE3-208

CAS#402473-54-5

Theoretical Analysis

MedKoo Cat#: 406814

Name: ONO-AE3-208

CAS#: 402473-54-5

Chemical Formula: C24H21FN2O3

Exact Mass: 404.1536

Molecular Weight: 404.44

Elemental Analysis: C, 71.27; H, 5.23; F, 4.70; N, 6.93; O, 11.87

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 495.00
10mg	USD 750.00
50mg	USD 1,650.00

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Synonym

ONO-AE3-208; ONO-AE-3-208; ONO-AE 3-208; AE 3-208; AE-3-208; AE3-208; ONO AE3 208

IUPAC/Chemical Name

4-cyano-2-[[2-(4-fluoro-1-naphthalenyl)-1-oxopropyl]amino]-benzenebutanoic acid

InChi Key

MTDIMKNAJUQTIO-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H21FN2O3/c1-15(18-11-12-21(25)20-7-3-2-6-19(18)20)24(30)27-22-13-16(14-26)9-10-17(22)5-4-8-23(28)29/h2-3,6-7,9-13,15H,4-5,8H2,1H3,(H,27,30)(H,28,29)

SMILES Code

O=C(O)CCCC1=CC=C(C#N)C=C1NC(C(C2=C3C=CC=CC3=C(F)C=C2)C)=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

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

Instruction

View handling instruction

Biological target:

ONO-AE3-208 is a selective and orally active EP4 receptor antagonist with a Ki of 1.3 nM.

In vitro activity:

The aim of this study was to analyze the association of EP4 with prostate cancer metastasis and the efficacy of ONO-AE3-208 for suppressing the metastasis. The expression levels of EP4 mRNA were evaluated in prostate cancer cell lines, LNCaP, and PC3. EP4 over-expressing LNCaP was established, and their cell invasiveness was compared with the control LNCaP (LNCaP/mock). The in vitro cell proliferation, invasion, and migration of these cells were examined under different concentrations of ONO-AE3-208. The in vitro cell invasion and migration were suppressed by ONO-AE3-208 in a dose-dependent manner without affecting cell proliferation. Reference: Cell Biochem Biophys. 2014 Sep;70(1):521-7. https://pubmed.ncbi.nlm.nih.gov/24744183/

In vivo activity:

The effect of intravesical administration of a selective EP4 antagonist (ONO-AE3-208; 30 μm) on bladder activity was evaluated in control rats and rats with prostatic inflammation. Intravesical application of ONO-AE3-208 (30 μm), but not vehicle application, significantly increased ICIs (intercontraction intervals) in rats with prostatic inflammation, whereas ONO-AE3-208 at this concentration did not significantly affect any cystometric values in control rats. Reference: BJU Int. 2019 Nov;124(5):883-891. https://pubmed.ncbi.nlm.nih.gov/31166645/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	74.18
	DMSO	34.6	85.53
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.24
	Ethanol	10.0	24.73

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 404.44 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. Luo Q, Liu M, Tan Y, Chen J, Zhang W, Zhong S, Pan J, Zheng Q, Gong L, Su L, Jia Z, Dou X. Blockade of prostaglandin E2 receptor 4 ameliorates peritoneal dialysis-associated peritoneal fibrosis. Front Pharmacol. 2022 Nov 11;13:1004619. doi: 10.3389/fphar.2022.1004619. PMID: 36438844; PMCID: PMC9691893. 3. Xu S, Zhang Z, Ogawa O, Yoshikawa T, Sakamoto H, Shibasaki N, Goto T, Wang L, Terada N. An EP4 antagonist ONO-AE3-208 suppresses cell invasion, migration, and metastasis of prostate cancer. Cell Biochem Biophys. 2014 Sep;70(1):521-7. doi: 10.1007/s12013-014-9951-2. PMID: 24744183. 4. Mizoguchi S, Wolf-Johnson AS, Ni J, Mori K, Suzuki T, Takaoka E, Mimata H, DeFranco DB, Wang Z, Birder LA, Yoshimura N. The role of prostaglandin and E series prostaglandin receptor type 4 receptors in the development of bladder overactivity in a rat model of chemically induced prostatic inflammation. BJU Int. 2019 Nov;124(5):883-891. doi: 10.1111/bju.14845. Epub 2019 Jun 26. PMID: 31166645; PMCID: PMC7327235. 2. Xu S, Ge JP, Zhou WQ, Zhang ZY. [Inhibitory effect of ONO-AE3-208 on the formation of bone metastasis of prostate cancer in mice]. Zhonghua Nan Ke Xue. 2014 Aug;20(8):684-9. Chinese. PMID: 25195362.

In vitro protocol:

In vivo protocol:

1. Mizoguchi S, Wolf-Johnson AS, Ni J, Mori K, Suzuki T, Takaoka E, Mimata H, DeFranco DB, Wang Z, Birder LA, Yoshimura N. The role of prostaglandin and E series prostaglandin receptor type 4 receptors in the development of bladder overactivity in a rat model of chemically induced prostatic inflammation. BJU Int. 2019 Nov;124(5):883-891. doi: 10.1111/bju.14845. Epub 2019 Jun 26. PMID: 31166645; PMCID: PMC7327235. 2. Xu S, Ge JP, Zhou WQ, Zhang ZY. [Inhibitory effect of ONO-AE3-208 on the formation of bone metastasis of prostate cancer in mice]. Zhonghua Nan Ke Xue. 2014 Aug;20(8):684-9. Chinese. PMID: 25195362.

1: Wang D, Fu L, Sun H, Guo L, DuBois RN. Prostaglandin E2 Promotes Colorectal Cancer Stem Cell Expansion and Metastasis in Mice. Gastroenterology. 2015 Dec;149(7):1884-1895.e4. doi: 10.1053/j.gastro.2015.07.064. Epub 2015 Aug 7. PubMed PMID: 26261008; PubMed Central PMCID: PMC4762503. 2: Säfholm J, Manson ML, Bood J, Delin I, Orre AC, Bergman P, Al-Ameri M, Dahlén SE, Adner M. Prostaglandin E2 inhibits mast cell-dependent bronchoconstriction in human small airways through the E prostanoid subtype 2 receptor. J Allergy Clin Immunol. 2015 Nov;136(5):1232-9.e1. doi: 10.1016/j.jaci.2015.04.002. Epub 2015 May 9. PubMed PMID: 25962903. 3: Terada N, Inoue T, Kamba T, Ogawa O. [Novel treatment for prostate cancer targeting prostaglandins]. Nihon Rinsho. 2014 Dec;72(12):2141-6. Japanese. PubMed PMID: 25518348. 4: Kassem KM, Clevenger MH, Szandzik DL, Peterson E, Harding P. PGE2 reduces MMP-14 and increases plasminogen activator inhibitor-1 in cardiac fibroblasts. Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:62-8. doi: 10.1016/j.prostaglandins.2014.09.002. Epub 2014 Sep 26. PubMed PMID: 25263346; PubMed Central PMCID: PMC4254138. 5: Xu S, Ge JP, Zhou WQ, Zhang ZY. [Inhibitory effect of ONO-AE3-208 on the formation of bone metastasis of prostate cancer in mice]. Zhonghua Nan Ke Xue. 2014 Aug;20(8):684-9. Chinese. PubMed PMID: 25195362. 6: Wang F, Lu X, Peng K, Du Y, Zhou SF, Zhang A, Yang T. Prostaglandin E-prostanoid4 receptor mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla. Hypertension. 2014 Aug;64(2):369-77. doi: 10.1161/HYPERTENSIONAHA.114.03654. Epub 2014 May 27. PubMed PMID: 24866147; PubMed Central PMCID: PMC4445967. 7: Mizuno R, Kamioka Y, Kabashima K, Imajo M, Sumiyama K, Nakasho E, Ito T, Hamazaki Y, Okuchi Y, Sakai Y, Kiyokawa E, Matsuda M. In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines. J Exp Med. 2014 Jun 2;211(6):1123-36. doi: 10.1084/jem.20132112. Epub 2014 May 19. PubMed PMID: 24842369; PubMed Central PMCID: PMC4042632. 8: Xu S, Zhang Z, Ogawa O, Yoshikawa T, Sakamoto H, Shibasaki N, Goto T, Wang L, Terada N. An EP4 antagonist ONO-AE3-208 suppresses cell invasion, migration, and metastasis of prostate cancer. Cell Biochem Biophys. 2014 Sep;70(1):521-7. doi: 10.1007/s12013-014-9951-2. PubMed PMID: 24744183. 9: Hayashi S, Kurata N, Yamaguchi A, Amagase K, Takeuchi K. Lubiprostone prevents nonsteroidal anti-inflammatory drug-induced small intestinal damage by suppressing the expression of inflammatory mediators via EP4 receptors. J Pharmacol Exp Ther. 2014 Jun;349(3):470-9. doi: 10.1124/jpet.114.213991. Epub 2014 Apr 8. PubMed PMID: 24713141. 10: Ren Y, D'Ambrosio MA, Garvin JL, Wang H, Carretero OA. Prostaglandin E2 mediates connecting tubule glomerular feedback. Hypertension. 2013 Dec;62(6):1123-8. doi: 10.1161/HYPERTENSIONAHA.113.02040. Epub 2013 Sep 23. PubMed PMID: 24060896; PubMed Central PMCID: PMC3882006. 11: Yoshikawa M, Ohinata K, Yamada Y. The pharmacological effects of novokinin; a designed peptide agonist of the angiotensin AT2 receptor. Curr Pharm Des. 2013;19(17):3009-12. PubMed PMID: 23176213. 12: Charo C, Holla V, Arumugam T, Hwang R, Yang P, Dubois RN, Menter DG, Logsdon CD, Ramachandran V. Prostaglandin E2 regulates pancreatic stellate cell activity via the EP4 receptor. Pancreas. 2013 Apr;42(3):467-74. doi: 10.1097/MPA.0b013e318264d0f8. PubMed PMID: 23090667; PubMed Central PMCID: PMC3600062. 13: Komatsu H, Enjouji S, Ito A, Ohama T, Sato K. Prostaglandin E(2) inhibits proteinase-activated receptor 2-signal transduction through regulation of receptor internalization. J Vet Med Sci. 2013;75(3):255-61. Epub 2012 Oct 15. PubMed PMID: 23064451. 14: Pöschke A, Kern N, Maruyama T, Pavenstädt H, Narumiya S, Jensen BL, Nüsing RM. The PGE(2)-EP4 receptor is necessary for stimulation of the renin-angiotensin-aldosterone system in response to low dietary salt intake in vivo. Am J Physiol Renal Physiol. 2012 Nov 15;303(10):F1435-42. doi: 10.1152/ajprenal.00512.2011. Epub 2012 Sep 19. PubMed PMID: 22993066. 15: 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. 16: Konya V, Üllen A, Kampitsch N, Theiler A, Philipose S, Parzmair GP, Marsche G, Peskar BA, Schuligoi R, Sattler W, Heinemann A. Endothelial E-type prostanoid 4 receptors promote barrier function and inhibit neutrophil trafficking. J Allergy Clin Immunol. 2013 Feb;131(2):532-40.e1-2. doi: 10.1016/j.jaci.2012.05.008. Epub 2012 Jun 15. PubMed PMID: 22704539. 17: Xin X, Majumder M, Girish GV, Mohindra V, Maruyama T, Lala PK. Targeting COX-2 and EP4 to control tumor growth, angiogenesis, lymphangiogenesis and metastasis to the lungs and lymph nodes in a breast cancer model. Lab Invest. 2012 Aug;92(8):1115-28. doi: 10.1038/labinvest.2012.90. Epub 2012 May 28. PubMed PMID: 22641101. 18: Cao RY, St Amand T, Li X, Yoon SH, Wang CP, Song H, Maruyama T, Brown PM, Zelt DT, Funk CD. Prostaglandin receptor EP4 in abdominal aortic aneurysms. Am J Pathol. 2012 Jul;181(1):313-21. doi: 10.1016/j.ajpath.2012.03.016. Epub 2012 May 15. PubMed PMID: 22595380. 19: Yokoyama U, Ishiwata R, Jin MH, Kato Y, Suzuki O, Jin H, Ichikawa Y, Kumagaya S, Katayama Y, Fujita T, Okumura S, Sato M, Sugimoto Y, Aoki H, Suzuki S, Masuda M, Minamisawa S, Ishikawa Y. Inhibition of EP4 signaling attenuates aortic aneurysm formation. PLoS One. 2012;7(5):e36724. doi: 10.1371/journal.pone.0036724. Epub 2012 May 3. PubMed PMID: 22570740; PubMed Central PMCID: PMC3343028. 20: Glenn JR, White AE, Iyu D, Heptinstall S. PGE(2) reverses G(s)-mediated inhibition of platelet aggregation by interaction with EP3 receptors, but adds to non-G(s)-mediated inhibition of platelet aggregation by interaction with EP4 receptors. Platelets. 2012;23(5):344-51. doi: 10.3109/09537104.2011.625575. Epub 2012 Mar 21. PubMed PMID: 22436052.