生物活性

• 描述Thromboxane synthase (TXAS) is a P450 epoxygenase that synthesizes thromboxane A2 (TXA2), a potent mediator of platelet aggregation, vasoconstriction and bronchoconstriction^[3]. Seratrodast (AA 2414) is an anti-asthmatic agent and a potent and selective thromboxane A2 receptor (TP) antagonist^[4]. Seratrodast inhibited peroxide-induced vasoconstriction in the human placenta, as well as peroxide- induced increases in the placental secretion rates of lipid peroxides and thromboxane, but only partially inhibited peroxide-induced increases in the placental secretion rate of prostacyclin^[5]. Seratrodast reduced the overproduction of TxB2 in both bronchoalveolar lavage fluid and lung tissues. Cigarette smoke exposure markedly increased AB/PAS-stained goblet cells and rat Muc5ac expression in the airway, which was significantly attenuated by seratrodast administration. The induced phosphorylation of ERK and p38 was also attenuated by seratrodast^[6]. The anti-asthmatic activity of AA-2414 has been studied in vivo and in vitro. Experimental allergic asthma was inhibited by orally administered AA-2414 in a dose-dependent manner. AA-2414, 0.08-1.25 mg/kg (p.o.), inhibited the bronchconstriction in guinea pigs induced by a prostaglandin endoperoxide analogue (U-46619), leukotriene D4 (LTD4), and platelet activating factor (PAF) with a long duration of action. The compound did not inhibit histamine-induced bronchoconstriction. AA-2414 reduced the induction of pulmonary inflation caused by LTD4 aerosol inhalation. AA-2414 competitively inhibited the contractile response to U-46619 in guinea pig tracheal and parenchymal strips and dog saphenous vein strips with pA2 values of 7.69, 8.29 and 6.79, respectively^[7].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02716246	Mucopolysaccharidosis Type 3 A... more >> Sanfilippo Syndrome Collapse <<	Phase 1 Phase 2	Recruiting	December 2020	United States, Ohio ... more >> Nationwide Children's Hospital Recruiting Columbus, Ohio, United States, 43205 Contact: Krista Kunkler    614-722-2238    krista.kunkler@nationwidechildrens.org    Australia, South Australia Women's and Children's Hospital Recruiting North Adelaide, South Australia, Australia, 5006 Contact: Louise Jaensch    08 8161 7295    louise.jaensch@sa.gov.au    Principal Investigator: Nicholas Smith, MD          Spain Hospital Clínico Universitario de Santiago Recruiting Santiago De Compostela, Spain, 15706 Contact: Maria Luz Couce, MD    +34 981 950 151    maria.luz.couce.pico@sergas.es    Contact: Maria Jose de Castro, MD    +34 981 955 627    maria.jose.de.castro.lopez@sergas.es Collapse <<

• 参考文献

• [1] Kurokawa T, Matsumoto T, et al. Antagonism of the human thromboxane A2 receptor by an anti-asthmatic agent AA-2414. Biol Pharm Bull. 1994 Mar;17(3):383-5.

  [2] Ashida Y, Matsumoto T, et al. A novel anti-asthmatic quinone derivative, AA-2414 with a potent antagonistic activity against a variety of spasmogenic prostanoids. Prostaglandins. 1989 Jul;38(1):91-112.

  [3] Plínio Cunha Sathler,et al. Human thromboxane synthase: comparative modeling and docking evaluation with the competitive inhibitors Dazoxiben and Ozagrel. J Enzyme Inhib Med Chem. 2014 Aug;29(4):527-31.

  [4] Ashida, Y., et al., A novel anti-asthmatic quinone derivative, AA-2414 with a potent antagonistic activity against a variety of spasmogenic prostanoids. Prostaglandins, 1989. 38(1): p. 91-112.

  [5] S W Walsh,et al. AA-2414, an antioxidant and thromboxane receptor blocker, completely inhibits peroxide-induced vasoconstriction in the human placenta. J Pharmacol Exp Ther. 1999 Jul;290(1):220-6.

  [6] Jing An,et al. Blocking of thromboxane A₂ receptor attenuates airway mucus hyperproduction induced by cigarette smoke. Eur J Pharmacol. 2013 Mar 5;703(1-3):11-7.

  [7] Y Ashida,et al. A novel anti-asthmatic quinone derivative, AA-2414 with a potent antagonistic activity against a variety of spasmogenic prostanoids. Prostaglandins.1989 Jul;38(1):91-112.

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