Discovery and characterization of a potent and selective EP4 receptor antagonist

Schiffler, Matthew A.; Chandrasekhar, Srinivasan; Fisher, M.; Kuklish, Steven L.; Wang, Xu-Shan; Warshawsky, Alan M.; York, Jeremy S.; Yu, Xiaopeng

doi:10.1016/j.bmcl.2015.05.091

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…,b,c, Schiffler et al. ). Reference EP4 antagonists CJ‐023,423 and CJ‐042,794 were prepared as described (Nakao et al.…”

Section: Methodsmentioning

confidence: 99%

“…,b,c; Schiffler et al. ). In this report, we describe the pharmacological characteristics of the molecules and show that they are highly effective in reducing the signs and symptoms in a variety of animal models of analgesia and inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…CJ-023,423, a selective EP4 antagonist has been shown to be efficacious in a prospective placebo controlled study for signs and symptoms of OA in dogs (Rausch-Derra et al 2016). Recently, we have described several EP4 antagonists that are highly selective and potent (Blanco et al 2016a,b,c;Schiffler et al 2015). In this report, we describe the pharmacological characteristics of the molecules and show that they are highly effective in reducing the signs and symptoms in a variety of animal models of analgesia and inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Analgesic and anti‐inflammatory properties of novel, selective, and potent EP4 receptor antagonists

Chandrasekhar

Oskins

et al. 2017

Pharmacology Res & Perspec

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Prostaglandin (PG) E2 is the key driver of inflammation associated with arthritic conditions. Inhibitors of PGE 2 production (NSAIDs and Coxibs) are used to treat these conditions, but carry significant side effect risks due to the inhibition of all prostanoids that play important physiological function. The activities of PGE 2 are transduced through various receptor sub‐types. Prostaglandin E2 type 4 receptor (EP4) is associated with the development of inflammation and autoimmunity. We therefore are interested in identifying novel EP4 antagonists to treat the signs and symptoms of arthritis without the potential side effects of PGE 2 modulators such as NSAIDs and Coxibs. Novel EP4 antagonists representing distinct chemical scaffolds were identified using a variety of in vitro functional assays and were shown to be selective and potent. The compounds were shown to be efficacious in animal models of analgesia, inflammation, and arthritis.

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“…,b,c, Schiffler et al. ). Reference EP4 antagonists CJ‐023,423 and CJ‐042,794 were prepared as described (Nakao et al.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analgesic and anti‐inflammatory properties of novel, selective, and potent EP4 receptor antagonists

Chandrasekhar

Oskins

et al. 2017

Pharmacology Res & Perspec

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Structural features of subtype-selective EP receptor modulators

Markovič

Jakopin

Dolenc

et al. 2017

Drug Discovery Today

136

125

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Prostaglandin E2 is a potent endogenous molecule that binds to four different G-protein-coupled receptors: EP1-4. Each of these receptors is a valuable drug target, with distinct tissue localisation and signalling pathways. We review the structural features of EP modulators required for subtype-selective activity, as well as the structural requirements for improved pharmacokinetic parameters. Novel EP receptor subtype selective agonists and antagonists appear to be valuable drug candidates in the therapy of many pathophysiological states, including ulcerative colitis, glaucoma, bone healing, B cell lymphoma, neurological diseases, among others, which have been studied in vitro, in vivo and in early phase clinical trials.

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Synthesis, anti-cancer activity and molecular docking studies of new nicotinamide containing EP4 antagonists

Ali

Chakraborty

Mondal

et al. 2022

Journal of Molecular Structure

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Discovery and characterization of a potent and selective EP4 receptor antagonist

Cited by 4 publications

References 15 publications

Analgesic and anti‐inflammatory properties of novel, selective, and potent EP4 receptor antagonists

Analgesic and anti‐inflammatory properties of novel, selective, and potent EP4 receptor antagonists

Structural features of subtype-selective EP receptor modulators

Synthesis, anti-cancer activity and molecular docking studies of new nicotinamide containing EP4 antagonists

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