Vanderslice Peter, Biediger Ronald J, Woodside Darren G, Berens Kurt L, Holland George W, Dixon Richard A F
Department of Biology, Encysive Pharmaceuticals, 7000 Fannin, 19th Floor, Houston, TX 77030, USA.
Pulm Pharmacol Ther. 2004;17(1):1-10. doi: 10.1016/j.pupt.2003.10.004.
Airway inflammation is a hallmark of respiratory diseases such as asthma and chronic obstructive pulmonary disease. Cell adhesion molecules play critical roles in the recruitment and migration of cells to sites of inflammation. Not surprisingly, these receptors have garnered the attention of the pharmaceutical industry as targets for the development of drugs to treat inflammatory and autoimmune diseases. Although several potential cell adhesion targets exist, development of compounds for pulmonary indications has centered around the selectins and the integrin VLA-4. In vitro and in vivo studies have implicated these receptors in the recruitment of inflammatory cells to the lung as well as to key cellular activation pathways. Several first generation compounds are currently in clinical development for asthma. Positive data from a phase II clinical trial using an inhaled formulation of a selectin antagonist has recently been reported. Initial results from clinical trials using first generation VLA-4 antagonists have been less promising but additional trials with more fully optimized compounds are underway. Results from these trials will provide insight into what the future holds for this exciting new class of drugs to treat pulmonary diseases.
气道炎症是哮喘和慢性阻塞性肺疾病等呼吸系统疾病的一个标志。细胞黏附分子在细胞向炎症部位的募集和迁移中起关键作用。不出所料，这些受体作为治疗炎症和自身免疫性疾病药物开发的靶点，已引起制药行业的关注。尽管存在几个潜在的细胞黏附靶点，但用于肺部适应症的化合物开发主要集中在选择素和整合素VLA-4上。体外和体内研究表明，这些受体参与了炎症细胞向肺部的募集以及关键的细胞激活途径。目前有几种第一代化合物正在进行哮喘的临床试验。最近有报道称，一项使用吸入型选择素拮抗剂的II期临床试验取得了阳性数据。使用第一代VLA-4拮抗剂的临床试验初步结果不太乐观，但正在进行更多经过充分优化的化合物的额外试验。这些试验的结果将为这类令人兴奋的新型治疗肺部疾病药物的未来发展提供见解。
