title: Investigational anti-inflammatory agents for the treatment of ischaemic brain injury.
abstract: Stroke is the third leading cause of death and the leading cause of disability in Western countries. To date, only approximately 2% of stroke patients are eligible for thrombolysis treatment with recombinant tissue plasminogen activator. The very limited options available for stroke treatment and recent disappointing clinical trials in stroke call for novel therapeutic approaches. Inflammation represents one of the key pathophysiological mechanisms for the progression of ischaemic stroke. Recent advances in preclinical models of stroke using investigational small molecular antagonists, neutralising antibodies/proteins or genetically altered gene functions against various inflammatory mediators suggest a great therapeutic potential of anti-inflammation for ischaemic stroke. The scope of the present review is to update the evidence for a role of inflammatory pathways in stroke and to summarise the investigational drugs currently available both in preclinical and clinical development for potential treatment of ischaemic stroke.
authors.affiliation: Bristol-Myers Squibb Company, Discovery Biology, 311 Pennington-Rocky Hill Road, Pennington, NJ 08534, USA. xinkang.wang@bms.com
authors.forename: Xinkang
authors.initials: X
authors.lastname: Wang
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors; D000072198:ADAM17 Protein; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; C483838:DPH-067517; D004791:Enzyme Inhibitors; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D051722:ADAM Proteins; D000072198:ADAM17 Protein