| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T85467 | ||||
| Target Name | Prostaglandin E2 receptor EP3 subtype | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | DG041 | Drug Info | IC50 = 5 nM | ||
| LAROPIPRANT | Drug Info | Ki = 892 nM | [528672] | ||
| 3-(2-((E)-3-phenylprop-1-enyl)phenyl)acrylic acid | Drug Info | Ki = 100 nM | [528393] | ||
| 3-(2-cinnamylphenyl)acrylic acid | Drug Info | Ki = 100 nM | [528393] | ||
| 3-(2-(4-methoxycinnamyl)phenyl)acrylic acid | Drug Info | Ki = 68 nM | [528393] | ||
| FR-181157 | Drug Info | Ki = 6800 nM | [527579] | ||
| 3-(2-(naphthalen-2-ylmethyl)phenyl)acrylic acid | Drug Info | Ki = 400 nM | [528393] | ||
| Action against Disease Model | DG041 | The bladder rhythmic contraction model and a bladder pain model measuring the visceromotor reflex (VMR) to urinary bladder distension (UBD) have been used to evaluate DG-041 in female rats. DG-041 (10 mg/kg), a peripherally restricted EP3 receptor antagonist, significantly reduced the frequency of bladder rhythmic contraction and inhibited the VMR response to bladder distension. DG-041 selectively attenuated responses of mechanosensitive afferent nerves to UBD, with strong suppression on the slow-conducting, high-threshold afferent fibers, with equivalent activity in thethree strains. We conclude that sensitization of afferent nerve activity was not one of the mechanisms of bladder hypersensitivity in SHR. EP3 receptors are involved in the regulation of bladder micturition and bladder nociception at the peripheral level. | [552831] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | The expression of matrix metalloproteinases (MMP)-9 and vascular endothelial growth factor (VEGF)-A was suppressed in NS-398-treated mice compared with PBS-treated mice. Lungs containing LLC colonies were markedly reduced in EP3 receptor knockout (EP3(-/-)) mice compared with WT mice. The expression of MMP-9 and VEGF-A was downregulated in metastatic lungs of EP3(-/-) mice. An immunohistochemical study revealed that MMP-9-expressing endothelial cells were markedly reduced in EP3(-/-) mice compared with WT mice | ||||
| References | |||||
| Ref 528672 | J Med Chem. 2007 Feb 22;50(4):794-806.Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524). | ||||
| Ref 528393 | Bioorg Med Chem Lett. 2006 Nov 1;16(21):5639-42. Epub 2006 Aug 22.Comparison between two classes of selective EP(3) antagonists and their biological activities. | ||||
| Ref 528393 | Bioorg Med Chem Lett. 2006 Nov 1;16(21):5639-42. Epub 2006 Aug 22.Comparison between two classes of selective EP(3) antagonists and their biological activities. | ||||
| Ref 528393 | Bioorg Med Chem Lett. 2006 Nov 1;16(21):5639-42. Epub 2006 Aug 22.Comparison between two classes of selective EP(3) antagonists and their biological activities. | ||||
| Ref 552831 | An excitatory role for peripheral EP3 receptors in bladder afferent function. Am J Physiol Renal Physiol. 2008 Aug;295(2):F585-94. doi: 10.1152/ajprenal.90273.2008. Epub 2008 Jun 18. | ||||
| Ref 527579 | Bioorg Med Chem Lett. 2005 Jul 1;15(13):3284-7.Metabolism investigation leading to novel drug design: orally active prostacyclin mimetics. Part 4. | ||||
| Ref 528393 | Bioorg Med Chem Lett. 2006 Nov 1;16(21):5639-42. Epub 2006 Aug 22.Comparison between two classes of selective EP(3) antagonists and their biological activities. | ||||
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