O'Neill Luke A J
School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland.
Nat Rev Drug Discov. 2006 Jul;5(7):549-63. doi: 10.1038/nrd2070. Epub 2006 Jun 9.
Inflammatory diseases are a major burden on humanity, despite recent successes with biopharmaceuticals. Lack of responsiveness and resistance to these drugs, delivery problems and cost of manufacture of biopharmaceuticals mean that the search for new anti-inflammatory agents continues. Progress in our understanding of inflammatory signalling pathways has identified new targets, notably in pathways involving NF-kappaB, p38 MAP kinase, T lymphocyte activation and JAK/STAT. Other targets such as transcription factor complexes and components of pathways activated by TNF, Toll-like receptors and Nod-like receptors also present possibilities, and might show efficacy without being limited by effects on host defence. The challenge is to place a value on one target relative to another, and to devise strategies to modulate them.
尽管生物制药最近取得了成功，但炎症性疾病仍是人类的一大负担。对这些药物缺乏反应性和耐药性、递送问题以及生物制药的制造成本意味着对新型抗炎药物的探索仍在继续。我们对炎症信号通路的理解取得了进展，确定了新的靶点，特别是在涉及核因子κB、p38丝裂原活化蛋白激酶、T淋巴细胞活化和JAK/STAT的通路中。其他靶点，如转录因子复合物以及由肿瘤坏死因子、Toll样受体和Nod样受体激活的通路成分也具有潜力，并且可能显示出疗效而不受对宿主防御影响的限制。挑战在于评估一个靶点相对于另一个靶点的价值，并设计调节它们的策略。
