ONO-AE2-227
ONO-AE2-227 is an orally active EP4 receptor antagonist. ONO-AE2-227 blocks PGE2-mediated EP4 signaling by competitively antagonizing PGE2-induced cAMP elevation, and binds to EP4/EP3 with mouse Ki values of 2.7/21 nM. ONO-AE2-227 reduces aberrant crypt foci and intestinal polyp development, and inhibits intestinal polyp formation. ONO-AE2-227 enhances LPS-induced TNF-alpha release from human alveolar macrophages by blocking endogenous PGE2, blocks PGE2-induced ICAM-1 expression and leukocyte-endothelial adhesion, and attenuates PGE2-induced monocyte adhesion to brain endothelial cells. ONO-AE2-227 can be used for research on colon cancer.
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- CAS No.: 357605-73-3
- Formule: C27H23NO3
- Masse moléculaire:409.49
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Activité biologique
Description
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EP4 2.7 nM (Ki) |
EP2 21 nM (Ki) |
TNF-α |
In Vitro
ONO-AE2-227 (10 mM; 24 h) reduces PGE2-induced ICAM-1 protein expression in primary cultured mouse brain endothelial cells[4].
ONO-AE2-227 (10 mM; 24 h) eliminates PGE2-induced U937 monocyte adhesion to bEnd.3 brain endothelial cells[4].
ONO-AE2-227 (2.7-21 nM) binds mouse EP4 with a Ki of 2.7 nM and mouse EP3 with a Ki of 21 nM in CHO cell binding assays, with 1000-fold lower affinity for mouse EP1, EP2, DP, FP, IP, and TP[2].
ONO-AE2-227 (10-160 nM) is a potent competitive EP4 antagonist (10 nM median inhibitory concentration for PGE2-induced cAMP increase) and a weak EP3 antagonist (160 nM IC50 for PGE2-induced calcium increase) in receptor-expressing cell assays[2].
ONO-AE2-227 (15 min) is a potent EP4 receptor antagonist (pKB 9.17) with high selectivity over EP2 in transfected HEK cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
ONO-AE2-227 (300 ppm; p.o.; ad libitum; from 6 weeks of age for 7 weeks) reduced the total number of intestinal polyps in Min mice, with the most significant reduction in the distal small intestine[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6Cr (male, 6 weeks of age)[2]
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Dosage:100 or 400 ppm in diet
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Administration:p.o.; ad libitum; from the day before first AOM until week 5
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Result:In AOM-treated mice (n = 8 per group), 400 ppm ONO-AE2-227 reduced ACFs/colon to 8.3 (67% of the AOM-alone group), and the mean number of ACs/focus was 1.5.
The 100 ppm ONO-AE2-227 group had 12.4 ACFs/colon and 1.5 mean ACs/focus and did not affect ACF formation.
No ACFs were observed in vehicle-injected mice with or without 400 ppm ONO-AE2-227.
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Animal Model:C57BL/6J-Min/+ (female, 6 weeks of age)[2]
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Dosage:300 ppm in diet
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Administration:p.o.; ad libitum; from 6 weeks of age for 7 weeks
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Result:In Min mice treated with 300 ppm ONO-AE2-227, total polyps/mouse were 42.2 (69% of the basal diet group).
By location, polyp numbers/mouse were: proximal small intestine 3.3 (83%), middle small intestine 14.2 (74%), distal small intestine 24.5 (65%), and colon 0.2 (40%).
The size distribution showed reduction in polyps measuring ≤1.0 mm in diameter but not those >1.0 mm in diameter.
Chemical Information
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CAS No. 357605-73-3
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Masse moléculaire 409.49
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Formule C27H23NO3
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SMILES
O=C(O)C=1C=CC=CC1CC=2C=CC=CC2NC(=O)C(C3=CC=CC=4C=CC=CC43)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ONO-AE2-227 Related Classifications
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