New approaches to the treatment of inflammatory disease : focus on small-molecule inhibitors of signal transduction pathways.

摘要: This‘state-of-the-art’ review specifically focuses on alternative signalling pathways deeply involved in acute and chronic inflammatory responses initiated by various pathological stimuli. The accumulated scientific knowledge has already revealed key biological targets, such as COX-2, related proinflammatory mediators (cytokines chemokines, interleukins [ILs], tumour necrosis factor [TNF]-α, migration inhibition [MIF], interferon [IFN]-ψ matrix metalloproteinases [MMPs]) implicated uncontrolled, destructive reaction. A number of physiologically active agents are currently approved for market or under investigation different clinical trials. However, recent findings have exposed the fatal adverse effects directly associated with drug therapy based COX-2 inhibition. Given these possible harmful outcomes, a range novel therapeutically relevant targets that include nuclear transcription (NF-κB), p38 mitogen-activated protein kinases (MAPK) Janus tyrosine signal transducers activators (JAK/STAT) received growing attention. Here we discuss progress identification development novel, clinically evaluated small-molecule regulators cascades promising anti-inflammatory drugs.