| Target Validation Information | |||||
|---|---|---|---|---|---|
| TTD ID | T18876 | ||||
| Target Name | Prostaglandin E2 receptor EP4 (PTGER4) | ||||
| Type of Target |
Clinical trial |
||||
| Drug Potency against Target | ONO-4819 | Drug Info | EC50 = 19 nM | [4] | |
| 3-(2-((E)-3-phenylprop-1-enyl)phenyl)acrylic acid | Drug Info | Ki = 4400 nM | [3] | ||
| 3-(2-(4-methoxycinnamyl)phenyl)acrylic acid | Drug Info | Ki = 6200 nM | [3] | ||
| 3-(2-(naphthalen-2-ylmethyl)phenyl)acrylic acid | Drug Info | Ki = 13000 nM | [3] | ||
| 3-(2-cinnamylphenyl)acrylic acid | Drug Info | Ki = 4400 nM | [3] | ||
| 8-aza-11-deoxyprostaglandin E1 | Drug Info | Ki = 4.5 nM | [1] | ||
| FR-181157 | Drug Info | Ki = 1020 nM | [2] | ||
| Action against Disease Model | ONO-4819 | Drug Info | Prostaglandin E(2) (PGE(2)) positively regulates bone resorption and formation mainly mediated through the EP(4) receptor, a subtype of PGE(2) receptors. ONO-4819, an EP(4) receptor-selective agonist, has been shown to increase bone vol uMe, density, and strength; however, the mechanism of these effects has yet to be fully elucidated. In vitro studies using the multipotent mesenchymal cell line C3H10T1/2 showed that ONO-4819 induced alkaline phosphatase (ALPase) activity and up-regulated the mRNA expression of ALPase and Osterix. In contrast, ONO-4819 reduced the mRNA expression of peroxisome proliferator-activated receptor ? (PPAR?) and inhibited adipocyte differentiation of C3H10T1/2 cells, which findings are consistent with the observation that the age-dependent increase in adipocyte n uMber in the bone marrow was significantly suppressed in the ONO-4819-treated animals. ONO-4819 also dose-dependently increased osteoclast-like cell formation in vitro, but the required concentrations were much higher than those to induce osteoblast differentiation. | [5] | |
| References | |||||
| REF 1 | Lactams as EP4 prostanoid receptor agonists. 3. Discovery of N-ethylbenzoic acid 2-pyrrolidinones as subtype selective agents. J Med Chem. 2004 Dec 2;47(25):6124-7. | ||||
| REF 2 | Discovery of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent and selective human prostaglandin EP(4) receptor antagonists. J Med Chem. 2005 May 5;48(9):3103-6. | ||||
| REF 3 | Comparison between two classes of selective EP(3) antagonists and their biological activities. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5639-42. | ||||
| REF 4 | Up-regulation of lymphocytic cholinergic activity by ONO-4819, a selective prostaglandin EP4 receptor agonist, in MOLT-3 human leukemic T cells. Vascul Pharmacol. 2004 Mar;41(2):51-8. | ||||
| REF 5 | Prostaglandin E(2) receptor EP(4)-selective agonist (ONO-4819) increases bone formation by modulating mesenchymal cell differentiation. Eur J Pharmacol. 2011 Jan 10;650(1):396-402. | ||||
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