2024年6月27日 · Ensifentrine（恩塞芬汀）是一款由Verona开发的靶向磷酸二酯酶-3 (PDE3)和磷酸二酯酶-4 (PDE4)的双靶点抑制剂，对PDE3的亲和度是PDE4的3440倍。作为双重PDE3/4 ...

2014年2月11日 · Developing an inhaled dual PDE3/4 inhibitor that is rapidly cleared from the systemic circulation, potentially with subtype specificity, may represent one strategy to improve the therapeutic index and also exhibit enhanced efficacy versus inhibition of either PDE3 or PDE4 alone, given the potential positive interactions with regard to anti ...

pde4:分布于被广泛表达于各种组织内。 其作用包括调节脑功能、调节单核细胞及巨噬细胞功能、血管平滑肌细胞增殖等； PDE5:分布于心脏、血小板、血管平滑肌、脑、肾、肺和骨骼肌;其主要作用包括调节血管收缩，尤其是阴茎和肺部血管的舒缩，同时通过调节 NO ...

2021年1月8日 · 大多数化合物表现出中等到高水平的人PDE3抑制活性(pIC 50 值在5.4~7.5之间), 同时也是PDE4的有效抑制剂(pIC 50 值在7.0~8.7之间)。构效关系的研究揭示, 连接基的种类和哒嗪酮上所连苯基取代基对PDE3与PDE4的抑制作用影响不大, 哒嗪酮的5位有甲基取代时活性较好, 且 …

2023年3月15日 · Phosphodiesterase 4 (PDE4) hydrolyzes cyclic adenosine monophosphate (cAMP) and plays a vital roles in many biological processes. PDE4 inhibitors have been widely studied as therapeutics for the treatment of various diseases, including asthma, chronic obstructive pulmonary disease (COPD) and psoriasis.

Ensifentrine是一款在研、潜在“first-in-class”的 磷酸二酯酶 3/4（PDE3/4）抑制剂，双重抑制机理使其能够凭借单个化合物同时实现支气管扩张和抗炎效果。在Verona公司对中重度COPD患者进行的2期临床研究中，ensifentrine对肺功能和包括呼吸困难在内的症状都有显著的 ...

2023年8月15日 · Rationale: Ensifentrine is a novel, selective, dual phosphodiesterase (PDE)3 and PDE4 inhibitor with bronchodilator and antiinflammatory effects. Replicate phase III trials of nebulized ensifentrine were conducted (ENHANCE-1 and ENHANCE-2) to assess these effects in patients with chronic obstructive pulmonary disease (COPD).

2024年7月2日 · 6月26日， Verona Pharma 公司开发的磷酸二酯酶3/4（PDE3/4）抑制剂Ensifentrine（恩塞芬汀）获得FDA批准用于治疗慢性阻塞性肺病（COPD）。 继 阿地溴铵 之后，COPD领域时隔12年终于迎来了一款创新机制产品。 说到磷酸二酯酶（PDE），大家可能并不陌生。 初代泛PDE抑制剂主要是 茶碱 类化合物，而这类药物在20世纪30年代便已成为COPD的症状控制药物。 而后经过几十年的发展，选择性更强的PDE抑制剂，例如PDE4抑制剂罗氟司特， …

Developing an inhaled dual PDE3/4 inhibitor that is rapidly cleared from the systemic circulation, potentially with subtype specificity, may represent one strategy to improve the therapeutic index and also exhibit enhanced efficacy versus inhibition of either PDE3 or PDE4 alone, given the potential positive interactions with regard to anti ...

3 天之前 · It is also interesting that when PDE3 is inhibited, PDE4 becomes more active and reduces the impact of catecholamines on cAMP and L-type Calcium currents (ICa,L) . The variations in enzyme properties help explain differences in how specific PDE4 isoforms are expressed and how they function in different species, as described below.