Malemud CJ, Blumenthal DE. Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives. World J Orthop 2014; 5(4): 496-503 [PMID: 25232525 DOI: 10.5312/wjo.v5.i4.496]
Corresponding Author of This Article
Charles J Malemud, PhD, Department of Medicine, Division of Rheumatic Diseases, The Arthritis Research Laboratory, Foley Medical Building, 2061 Cornell Road, Cleveland, OH 44106-5076, United States. cjm4@cwru.edu
Research Domain of This Article
Rheumatology
Article-Type of This Article
Topic Highlight
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World J Orthop. Sep 18, 2014; 5(4): 496-503 Published online Sep 18, 2014. doi: 10.5312/wjo.v5.i4.496
Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives
Charles J Malemud, David E Blumenthal
Charles J Malemud, David E Blumenthal, The Arthritis Research Laboratory, Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University, Cleveland, OH 44106-5076, United States
Charles J Malemud, David E Blumenthal, Department of Anatomy, Case Western Reserve University, Cleveland, OH 44106-5076, United States
Charles J Malemud, David E Blumenthal, School of Medicine, Division of Rheumatology, Veteran’s Administration Medical Center, Cleveland, OH 44106, United States
Author contributions: Malemud CJ and Blumenthal DE solely contributed to this paper.
Supported by A contract from Genentech/Roche Group and the Case Western Reserve University School of Medicine Visual Sciences Research Core, No. P30 EY-011373
Correspondence to: Charles J Malemud, PhD, Department of Medicine, Division of Rheumatic Diseases, The Arthritis Research Laboratory, Foley Medical Building, 2061 Cornell Road, Cleveland, OH 44106-5076, United States. cjm4@cwru.edu
Telephone: +1-216-8447846 Fax: +1-216-8442288
Received: January 11, 2014 Revised: June 5, 2014 Accepted: June 20, 2014 Published online: September 18, 2014
Core Tip
Core tip: Signal transduction is a regulator of gene expression in cells. Janus kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling is activated by pro-inflammatory cytokines which contributes to immune-mediated inflammation in rheumatoid arthritis. Medicinal chemistry was employed to develop JAK small molecule inhibitors for determining their clinical efficacy in active rheumatoid arthritis patients. Tofacitinib, a JAK small molecule inhibitor, is now generally used to treat moderate to severe rheumatoid arthritis patients who have not adequately responded to disease-modifying anti-rheumatic drugs or various biologic agents. The clinical efficacy of JAK small molecule inhibitors provides the impetus for future drug discovery targeted at other signal transduction pathways in rheumatoid arthritis.
