NDLI: SB1578, a novel inhibitor of JAK2, FLT3, and c-Fms for the treatment of rheumatoid arthritis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dymock, Brian W. William, Anthony D. Jayaraman, Ramesh Ethirajulu, Kantharaj Hart, Stefan Goh, Kee Chuan Madan, Babita Wood, Jeanette M.
Description	Author Affiliation: Madan B ( S*BIO Pte. Ltd., Singapore 117528. babitamadan@yahoo.com)
Abstract	SB1578 is a novel, orally bioavailable JAK2 inhibitor with specificity for JAK2 within the JAK family and also potent activity against FLT3 and c-Fms. These three tyrosine kinases play a pivotal role in activation of pathways that underlie the pathogenesis of rheumatoid arthritis. SB1578 blocks the activation of these kinases and their downstream signaling in pertinent cells, leading to inhibition of pathological cellular responses. The biochemical and cellular activities of SB1578 translate into its high efficacy in two rodent models of arthritis. SB1578 not only prevents the onset of arthritis but is also potent in treating established disease in collagen-induced arthritis mice with beneficial effects on histopathological parameters of bone resorption and cartilage damage. SB1578 abrogates the inflammatory response and prevents the infiltration of macrophages and neutrophils into affected joints. It also leads to inhibition of Ag-presenting dendritic cells and inhibits the autoimmune component of the disease. In summary, SB1578 has a unique kinase spectrum, and its pharmacological profile provides a strong rationale for the ongoing clinical development in autoimmune diseases.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-10-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Arthritis, Experimental Drug Therapy Immunology Heterocyclic Compounds With 4 Or More Rings Administration & Dosage Janus Kinase 2 Antagonists & Inhibitors Receptor, Macrophage Colony-stimulating Factor Fms-like Tyrosine Kinase 3 Animals Pathology Arthritis, Rheumatoid Disease Models, Animal Therapeutic Use Mice Mice, Inbred C57bl Rats, Inbred Lew Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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