Reactome | PTGIR binds PTGIR agonists

PTGIR binds PTGIR agonists

Stable Identifier

R-HSA-9726949

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

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The endogenous prostanoid prostacyclin is continuously produced by healthy vascular endothelial cells and inhibits platelet activation through interaction with the Gs-coupled prostacyclin receptor PTGIR. Prostacyclin prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation) and is also an effective vasodilator.

Pulmonary arterial hypertension (PAH) is a chronic, progressive, multifactorial disease. The endothelin, nitric oxide (NO), and prostacyclin pathways are involved in PAH and combined therapies that target each of these pathways are currently recommended. The PTGIR agonists iloprost and treprostinil (Whittle et al. 2012) are indicated for PAH (Gąsecka et al. 2021). Selexipag is a novel oral PTGIR agonist drug with vasodilatory and antiproliferative effects. It is the prodrug, metabolised to the active form MRE-269 (Kuwano et al. 2007). Selexipag is well tolerated and safe when used to treat PAH in children (Hansmann et al. 2020, Bravo-Valenzuela et al. 2021).

Literature References

PubMed ID	Title	Journal	Year
17545310	2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug Kuwano, K, Hashino, A, Asaki, T, Hamamoto, T, Yamada, T, Okubo, K, Kuwabara, K	J. Pharmacol. Exp. Ther.	2007
10634944	The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs Abramovitz, M, Adam, M, Boie, Y, Carrière, M, Denis, D, Godbout, C, Lamontagne, S, Rochette, C, Sawyer, N, Tremblay, NM, Belley, M, Gallant, M, Dufresne, C, Gareau, Y, Ruel, R, Juteau, H, Labelle, M, Ouimet, N, Metters, KM	Biochim. Biophys. Acta	2000
22480736	Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist Whittle, BJ, Silverstein, AM, Mottola, DM, Clapp, LH	Biochem. Pharmacol.	2012