Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug 英文参考文献.docVIP

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Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug 英文参考文献.doc

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Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug 英文参考文献

Available online /content/11/1/R12 Research article Open Access Vol 11 No 1 Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug Grant R Zimmermann, William Avery, Alyce L Finelli, Melissa Farwell, Christopher C Fraser and Alexis A Borisy CombinatoRx, Incorporated, First Street, Cambridge, MA 02142, USA Corresponding author: Grant R Zimmermann, gzimmermann@ Received: 13 Sep 2008 Revisions requested: 5 Nov 2008 Revisions received: 1 Dec 2008 Accepted: 26 Jan 2009 Published: 26 Jan 2009 Arthritis Research Therapy 2009, 11:R12 (doi:10.1186/ar2602) This article is online at: /content/11/1/R12 ? 2009 Zimmermann et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Glucocorticoids are a mainstay of anti- acute lipopolysaccharide-induced endotoxemia and delayed- type hypersensitivity, and in chronic models of collagen-induced and adjuvant-induced arthritis, the combination produced anti- inflammatory activity that required only a subtherapeutic dose of inflammatory therapy, but significant adverse effects ultimately limit their utility. Previous efforts to design glucocorticoid structures with an increased therapeutic window have focused on dissociating anti-inflammatory transcriptional repression from adverse effects primarily driven by transcriptional activation. An alternative to this medicinal chemistry approach is a systems biology based strategy that seeks to amplify selectively the anti- inflammatory activity of very low dose glucocorticoid in immune cells without modulating alternative cellular networks that mediate glucocorticoid toxicity. prednisolone. The immune-specific amplification of predn