Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CPC-211 is under development by Questcor (formerly Cypros) as a potential treatment for stroke and closed head injury. Phase II trials have commenced for both indications. In June 1999, it was granted Orphan Drug status [329979]. In July 1998, CPC-211 received expedited development status by the FDA, following a review of the company's data and clinical plan for the development of CPC-211 to treat acute head injury [291130]. CPC-211 stimulates the action of pyruvate dehydrogenase, reducing the build up of lactic acid which may cause brain damage after stroke. It diverts the lactate production into acetyl-CoA which is a beneficial metabolite. CPC-211 crosses the blood-brain barrier. Preclinical studies involving both stroke and head injury models have shown that CPC-211 (25 to 200 mg/kg iv) effected a significant reduction in brain lactate levels [328231].
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PMID:CPC-211 (Questcor). 1609 29

Acadesine is an adenosine receptor agonist (ARA) in development for the treatment of ischaemia-reperfusion injury and chronic lymphocytic leukaemia. Schering-Plough is developing the compound as a cardioprotective agent in ischaemia-reperfusion injury. Avancell and Protherics are co-developing acadesine for the treatment of B-cell chronic lymphocytic leukaemia (B-CLL). Clinical development is underway for both indications. In January 2005, PeriCor Therapeutics obtained a sublicense for the worldwide rights to acadesine and three additional ARA compounds from Dr Mangano who was a founder of the company. Dr Mangano acquired the license of worldwide rights for acadesine from Metabasis in November 2000.Previously, in December 1997, all intellectual property rights and data covering acadesine and related ARAs for cardiovascular and cerebrovascular disorders were transferred from the original developer, Gensia Sicor (SICOR), to Metabasis Therapeutics in an asset-liability transfer agreement.Schering-Plough intends to conduct a randomized, placebo-controlled phase III trial, which is required for regulatory approval. The trial will further evaluate acadesine in patients deemed to be at high risk of ischaemic heart disorders. Patients will have either undergone coronary artery bypass graft surgery, or have a history of cardiovascular events (heart attack or stroke). Protherics presented 2-year mortality results from a study of acadesine, investigating long-term mortality after perioperative myocardial infarction, at the 55th Scientific Session of the American College of Cardiology in 2006.Previously, Gensia Sicor conducted clinical trials of acadesine in Canada, the EU and the US; results of these trials were inconclusive. Acadesine has been shown to selectively cause the death of B-cells, whilst sparing T-cells when administered to blood samples taken from patients with B-CLL. Orphan drug status has been granted for acadesine in the EU for the treatment of B-cell chronic lymphocytic leukaemia.
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PMID:Acadesine: AICA riboside, ARA 100, arasine, GP 1 110. 1845 69

Neuroinflammation plays a pivotal part in the pathogenesis of stroke. Orphan nuclear receptor NR4A1 is involved in the inflammatory response of microglia and macrophages. In this study, we discovered an old drug, 9-aminoacridine (9-AA), as a novel NR4A1 activator from our in-house FDA-approved drug library, which exhibited anti-inflammatory activities through an NR4A1/IL-10/SOCS3 signaling pathway and modulated the microglia activation. To improve the druggability of 9-AA, different liposomal formulations were screened and investigated. 9-AA-loaded liposome (9-AA/L) was prepared to reduce the adverse effect of 9-AA. Furthermore, 9-AA-loaded PEG/cRGD dual-modified liposome (9-AA/L-PEG-cRGD) was obtained, which displayed prolonged circulation, improved biodistribution, and increased brain accumulation. In the transient middle cerebral artery occlusion (tMCAO) rat model, 9-AA/L-PEG-cRGD significantly reduced brain infarct area, ameliorated ischemic brain injury, and promoted long-term neurological function recovery. This "from drug discovery to drug delivery" methodology provides a potential therapeutic strategy using the liposomal 9-AA, the NR4A1 activator to suppress neuroinflammation for treatment of ischemic stroke.
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PMID:Liposomal 9-Aminoacridine for Treatment of Ischemic Stroke: From Drug Discovery to Drug Delivery. 3203 6