Ensifentrine

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Ensifentrine 是一种 PDE3/4 抑制剂，尽管其对 PDE3 的亲和力 (IC50: 0.4 nM) 比对 PDE4 (IC50: 1479 nM) 的亲和力高 3,440 倍，PDE4 正在临床开发中，用于治疗哮喘和 COPD，并且有可能囊性纤维化。

Ensifentrine is a PDE3/4 inhibitor, although its affinity for PDE3(IC50: 0.4 nM) is 3,440 times higher than that for PDE4(IC50: 1479 nM), that is under clinical development for the treatment of asthma and COPD and, potentially, cystic fibrosis.(In Vitro):Electrical field stimulation-induced contraction of guinea pig superfused isolated tracheal preparations was significantly inhibited by Ensifentrine (10 microM) (percentage control; 93 +/- 1.2). Contractile responses were suppressed for up to 12 h after termination of superfusion with Ensifentrine demonstrating a long duration of action. Ensifentrine4 inhibited, in a concentration-dependent manner, lipopolysaccharide-induced tumor necrosis factor alpha release from human monocytes [IC50; 0.52 microM (0.38-0.69)] and proliferation of human mononuclear cells to phytohemagglutinin [IC50; 0.46 microM (0.24-0.9)].(In Vivo):Ensifentrine administered orally significantly inhibited eosinophil recruitment following antigen challenge in ovalbumin-sensitized guinea pigs. Likewise, inhalation of dry powder containing Ensifentrine by conscious guinea pigs (25% in micronized lactose) 1.5 h before antigen exposure significantly inhibited the recruitment of eosinophils to the airways. Exposure of conscious guinea pigs to inhalation of dry powder containing Ensifentrine (2.5%) and RPL565 (25%) in micronized lactose significantly inhibited histamine-induced plasma protein extravasation in the trachea and histamine-induced bronchoconstriction over a 5.5-h period.

Ensifentrine (RPL-554) inhibits, in a concentration-dependent manner, lipopolysaccharide-induced TNF-α release from human monocytes (IC50 of 0.52 μM) and proliferation of human mononuclear cells to phytohemagglutinin (IC50 of 0.46 μM). Electrical field stimulation-induced contraction of guinea pig superfused isolated tracheal preparations is significantly inhibited by Ensifentrine (10 μM). Contractile responses are suppressed for up to 12 h after termination of superfusion with RPL-554 demonstrating a long duration of action.

Ensifentrine (RPL-554; 10 mg/kg; Oral administration; once) significantly inhibits eosinophil recruitment following antigen challenge in ovalbumin-sensitized guinea pigs.The inhalation of dry powder containing Ensifentrine by conscious guinea pigs (25% in micronized lactose) 1.5 h before antigen exposure significantly inhibits the recruitment of eosinophils to the airways.Exposure of conscious guinea pigs to inhalation of dry powder containing Ensifentrine (2.5%) in micronized lactose significantly inhibits histamine-induced plasma protein extravasation in the trachea and histamine-induced bronchoconstriction over a 5.5-h period. Animal Model:Male Dunkin Hartley guinea pigs (200-300 g) injected with ovalbumin.Dosage:10 mg/kg.Administration:Oral administration; once Result:Significantly inhibits eosinophil recruitment following antigen challenge in ovalbumin-sensitized guinea pigs.

Ensifentrina | Ensifentrinum

Angiogenesis

PDE

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1884461-72-6

477.565

C26H31N5O4

>98% (HPLC)

In Vitro:?DMSO : 25 mg/mL (52.35 mM)

COc1cc2CCn3c(c\c(=N/c4c(C)cc(C)cc4C)n(CCNC(N)=O)c3=O)-c2cc1OC

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(-20℃)

With Ice Pack

≥ 2 years