"目录号: HY-14655
NF-κBAutophagy-
Sulfasalazine是治疗类风湿关节炎和溃疡性结肠炎的药物。
NF-κBAutophagy
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生物活性
Description
Sulfasalazine is a drug for the treatment of rheumatoid arthritis and ulcerative colitis.
In Vitro
Treatment of SW620 colon cells with sulfasalazine inhibits TNFα-, LPS-, or phorbol ester-induced NFκB activation. NFκB–dependent transcription is inhibited by sulfasalazine at micro- to millimolar concentrations. TNFα-induced nuclear translocation of NFκB is prevented by sulfasalazine through inhibition of IκBα degradation[1]. Pre‐incubation with 5 mM of sulfasalazine alone significantly increases basal mRNA expression of all pro‐inflammatory cytokines with levels of IL‐6 mRNA increased by 80‐fold compared with vehicle control[2]. Once digested, sulfasalazine is cleaved into sulfapyridine and 5-aminosalicylic acid by colonic bacteria, and the latter, too, is reported to suppress NF-kappaB activity[3].
In Vivo
At low doses (0.25 mM), SAS is able to suppress glioma growth by over 60% compared to untreated controls[3].
Clinical Trial
NCT00637780
Pfizer
Arthritis, Juvenile Rheumatoid
June 2010
Phase 4
NCT01577966
University of Alabama at Birmingham
Brain Tumor
January 2012
NCT01312129
The Mind Research Network
Alcohol Dependence
March 2010
NCT00554203
Boston University
Coronary Artery Disease
July 2003
NCT01198145
Alliance for Clinical Trials in Oncology-National Cancer Institute (NCI)
Diarrhea-Gastrointestinal Complications-Unspecified Adult Solid Tumor, Protocol Specific
April 2011
Phase 3
NCT01659242
Singapore General Hospital
Rheumatoid Arthritis
July 2012
Phase 4
NCT01667029
Massachusetts General Hospital
Painful Neuropathy
May 2013
Phase 2
NCT00844142
Charite University, Berlin, Germany-Wyeth is now a wholly owned subsidiary of Pfizer
Moderate to Severe Active Axial Spondyloarthritis
November 2005
Phase 2
NCT03012763
University Medicine Greifswald
Pharmacokinetics-Magnetic Resonance Imaging-Administration, Oral
April 2016
Phase 1
NCT00579878
University of Nebraska
Rheumatoid Arthritis
December 1999
Phase 3
NCT02434861
Tesaro, Inc.
Chemotherapy-induced Nausea and Vomiting
May 2015
Phase 1
NCT02930343
Jawaharlal Institute of Postgraduate Medical Education & Research
Rheumatoid Arthritis
September 2016
Phase 4
NCT02456363
Chung Shan Medical University
Ankylosing Spondylitis
November 2009
Phase 2
NCT02638896
Zhixiang Huang-Health and Family Planning Commission of Guangdong
Ankylosing Spondylitis
January 2016
Phase 4
NCT00405275
VA Office of Research and Development-Canadian Institutes of Health Research (CIHR)-Rheumatoid Arthritis Investigational Network (RAIN)-National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Rheumatoid Arthritis
July 2007
NCT02374021
Brigham and Women's Hospital-Columbia University
Arthritis, Rheumatoid
July 2016
Phase 4
NCT00422227
Wyeth is now a wholly owned subsidiary of Pfizer
Rheumatoid Arthritis
June 2007
Phase 4
NCT00259610
University of Alabama at Birmingham-Amgen-Barr Laboratories-Pfizer
Rheumatoid Arthritis
May 2004
Phase 4
NCT00889694
Sun Yat-sen University
Early Ankylosing Spondylitis
October 2008
Phase 2-Phase 3
NCT00521924
Merck Sharp & Dohme Corp.-AESCA Pharma GmbH
Rheumatoid Arthritis
June 2007
Phase 3
NCT01709578
Sanofi
Rheumatoid Arthritis
October 2012
Phase 3
NCT01941095
Hoffmann-La Roche
Rheumatoid Arthritis
November 2013
Phase 3
NCT01768572
Sanofi-Regeneron Pharmaceuticals
Rheumatoid Arthritis
March 2013
Phase 3
NCT02057250
Sanofi-Regeneron Pharmaceuticals
RA
March 2014
Phase 3
NCT02373202
Sanofi-Regeneron Pharmaceuticals
Rheumatoid Arthritis
February 2015
Phase 3
NCT02433184
University of Leeds
Rheumatoid Arthritis
July 2011
Phase 4
NCT01596777
University Medicine Greifswald
Intestinal Obstruction
January 2010
Phase 1
NCT01596764
University Medicine Greifswald
Intestinal Obstruction
May 2011
Phase 1
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References
[1].Wahl C, et al. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest. 1998 Mar 1;101(5):1163-74.
[2].Sykes L, et al. Sulfasalazine augments a pro-inflammatory response in interleukin-1β-stimulated amniocytes and myocytes. Immunology. 2015 Dec;146(4):630-44.
[3].Chung WJ, et al. Sulfasalazine inhibits the growth of primary brain tumors independent of nuclear factor-kappaB. J Neurochem. 2009 Jul;110(1):182-93.