セレキシパグ 化学特性,用途語,生産方法
効能
血圧降下薬, 血管拡張薬, プロスタグランジンI2受容体作動薬
商品名
ウプトラビ (日本新薬)
説明
Selexipag and its active
metabolite, the corresponding carboxylic acid, are nonprostanoid
prostaglandin I2 (PGI-2) receptor agonists. The N-methylsulfonamide within selexipag is hydrolyzed
to the corresponding carboxylic acid in vivo by hepatic
microsomes at a rate which provides a slow-release
pharmacological effect. The compound was originally
discovered by Nippon Shinyaki and later licensed to Actelion
for development. The drug was approved in 2015 and first
launched for the oral treatment of pulmonary arterial
hypertension (PAH) in the U.S. in 2016 to delay disease
progression and reduce the risk of hospitalization.
使用
Selexipag is an orally available, highly selective, long-acting prostacyclin (IP) receptor agonist prodrug. It is a potential drug for the treatment of various vascular disorders such as pulmonary arterial hypertension and arteriosclerosis obliterans.
定義
ChEBI: Selexipag is a member of the class of pyrazines that is N-(methanesulfonyl)-2-{4-[(propan-2-yl)(pyrazin-2-yl)amino]butoxy}acetamide carrying two additional phenyl substituents at positions 5 and 6 on the pyrazine ring. An orphan drug used for the treatment of pulmonary arterial hypertension. It is a prodrug for ACT-333679 (the free carboxylic acid). It has a role as an orphan drug, a prostacyclin receptor agonist, a platelet aggregation inhibitor, a vasodilator agent and a prodrug. It is a monocarboxylic acid amide, an ether, a member of pyrazines, an aromatic amine, a tertiary amino compound and a N-sulfonylcarboxamide. It is functionally related to an ACT-333679.
生物活性
Prostaglandin I2 (PGI2) is a potent vasorelaxant and inhibitor of human platelet aggregation that mediates its actions by binding to a specific G protein- coupled receptor, the IP receptor, on the surface of endothelial cells and platelets. The IP receptor also participates in signal transduction of the pain response, cardioprotection, and inflammation. Selexipag(NS-304) is a prodrug of the active form of MRE-269, which is a potent and selective agonist for the human IP receptor with a Ki value of 20 nM. In contrast to prostaglandin I2, which has a half-life of 30 seconds to a few minutes in vivo, NS-304 is long-acting. Plasma concentrations of MRE-269 remain near peak levels for more than eight hours in rats and dogs after NS-304 was administered orally.
臨床応用
Selexipag was approved by the United States FDA on December 22, 2015 for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and reduce risk of hospitalization.
Selective IP receptor agonist:
Treatment of pulmonary arterial hypertension.
セレキシパグ 上流と下流の製品情報
原材料
準備製品