原创力文档selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug糖皮质激素抗炎活动的选择性放大通过协同多目标组合药物的作用.pdfVIP
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selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug糖皮质激素抗炎活动的选择性放大通过协同多目标组合药物的作用
Available online /content/11/1/R12
Vol 11 No 1 Open Access
Research article
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-
inflammatory therapy, but significant adverse effects ultimately type hypersensitivity, and in chronic models of collagen-induced
limit their utility. Previous efforts to design glucocorticoid and adjuvant-induced arthritis, the combination produced anti-
structures with an increased therapeutic window have focused inflammatory activity that required only a subtherapeutic dose of
on dissociating anti-inflammatory transcriptional repression from prednisolone. The immune-specific amplification of
adverse effects
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