Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis
Background: In the last few years, significant progress has been made in understanding the pathogenic mechanisms and in defining the role of relevant cells and molecules in the pathophysiology of rheumatoid arthritis (RA). Various therapies, both biological (anti-TNF, anti-interleukins [e.g., IL-1])...
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Veröffentlicht in: | Expert opinion on investigational drugs 2008-05, Vol.17 (5), p.641-659 |
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description | Background: In the last few years, significant progress has been made in understanding the pathogenic mechanisms and in defining the role of relevant cells and molecules in the pathophysiology of rheumatoid arthritis (RA). Various therapies, both biological (anti-TNF, anti-interleukins [e.g., IL-1]) and small molecule inhibitors have been explored for the treatment of RA. Objective: To date, no single signaling pathway inhibitor as wide acting as the corticosteroids, is known. However, treatment with corticosteroids is also associated with allied side effects. Despite a lot of efforts in the category of small molecule inhibitors, no inhibitor is available to deal with RA at both fronts (inflammation and tissue damage), without causing immense side effects. Method: This present review explores the role of spleen tyrosine kinase (Syk) in the pathogenesis of RA and also discusses how it may meet the present day therapeutic requirements for the treatment of RA. This review gives an in-depth discussion on the role of Syk signaling in RA, the possibilities of using Syk as a target and also discusses the possible side effects that could be associated with its inhibition. Conclusion: We propose Syk inhibition as a potential therapeutic approach for the treatment of RA. |
doi_str_mv | 10.1517/13543784.17.5.641 |
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Various therapies, both biological (anti-TNF, anti-interleukins [e.g., IL-1]) and small molecule inhibitors have been explored for the treatment of RA. Objective: To date, no single signaling pathway inhibitor as wide acting as the corticosteroids, is known. However, treatment with corticosteroids is also associated with allied side effects. Despite a lot of efforts in the category of small molecule inhibitors, no inhibitor is available to deal with RA at both fronts (inflammation and tissue damage), without causing immense side effects. Method: This present review explores the role of spleen tyrosine kinase (Syk) in the pathogenesis of RA and also discusses how it may meet the present day therapeutic requirements for the treatment of RA. This review gives an in-depth discussion on the role of Syk signaling in RA, the possibilities of using Syk as a target and also discusses the possible side effects that could be associated with its inhibition. Conclusion: We propose Syk inhibition as a potential therapeutic approach for the treatment of RA.</description><identifier>ISSN: 1354-3784</identifier><identifier>EISSN: 1744-7658</identifier><identifier>DOI: 10.1517/13543784.17.5.641</identifier><identifier>PMID: 18447591</identifier><language>eng</language><publisher>England: Informa UK Ltd</publisher><subject>Animals ; Antirheumatic Agents - adverse effects ; Antirheumatic Agents - pharmacology ; Antirheumatic Agents - therapeutic use ; arthritis ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - enzymology ; Arthritis, Rheumatoid - immunology ; Clinical Trials as Topic ; corticosteroid ; Enzyme Inhibitors - adverse effects ; Enzyme Inhibitors - pharmacology ; Enzyme Inhibitors - therapeutic use ; Humans ; inflammation ; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors ; kinase ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Protein-Tyrosine Kinases - biosynthesis ; R406 ; R788 ; Spleen - enzymology ; Spleen - immunology ; Syk ; Syk Kinase</subject><ispartof>Expert opinion on investigational drugs, 2008-05, Vol.17 (5), p.641-659</ispartof><rights>Informa UK Ltd 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-20c65152d70b6ef6e3c5baf63b514692a15242ce4ca7277199c404bf8169efa43</citedby><cites>FETCH-LOGICAL-c435t-20c65152d70b6ef6e3c5baf63b514692a15242ce4ca7277199c404bf8169efa43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1517/13543784.17.5.641$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1517/13543784.17.5.641$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,59620,59726,60409,60515</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18447591$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bajpai, Malini</creatorcontrib><creatorcontrib>Chopra, Puneet</creatorcontrib><creatorcontrib>Dastidar, Sunanda G</creatorcontrib><creatorcontrib>Ray, Abhijit</creatorcontrib><title>Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis</title><title>Expert opinion on investigational drugs</title><addtitle>Expert Opin Investig Drugs</addtitle><description>Background: In the last few years, significant progress has been made in understanding the pathogenic mechanisms and in defining the role of relevant cells and molecules in the pathophysiology of rheumatoid arthritis (RA). Various therapies, both biological (anti-TNF, anti-interleukins [e.g., IL-1]) and small molecule inhibitors have been explored for the treatment of RA. Objective: To date, no single signaling pathway inhibitor as wide acting as the corticosteroids, is known. However, treatment with corticosteroids is also associated with allied side effects. Despite a lot of efforts in the category of small molecule inhibitors, no inhibitor is available to deal with RA at both fronts (inflammation and tissue damage), without causing immense side effects. Method: This present review explores the role of spleen tyrosine kinase (Syk) in the pathogenesis of RA and also discusses how it may meet the present day therapeutic requirements for the treatment of RA. This review gives an in-depth discussion on the role of Syk signaling in RA, the possibilities of using Syk as a target and also discusses the possible side effects that could be associated with its inhibition. Conclusion: We propose Syk inhibition as a potential therapeutic approach for the treatment of RA.</description><subject>Animals</subject><subject>Antirheumatic Agents - adverse effects</subject><subject>Antirheumatic Agents - pharmacology</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>arthritis</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Arthritis, Rheumatoid - enzymology</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Clinical Trials as Topic</subject><subject>corticosteroid</subject><subject>Enzyme Inhibitors - adverse effects</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Humans</subject><subject>inflammation</subject><subject>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</subject><subject>kinase</subject><subject>Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Protein-Tyrosine Kinases - biosynthesis</subject><subject>R406</subject><subject>R788</subject><subject>Spleen - enzymology</subject><subject>Spleen - immunology</subject><subject>Syk</subject><subject>Syk Kinase</subject><issn>1354-3784</issn><issn>1744-7658</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhiMEoqXwA7ggn7hlseOvBLigigJSJQ4tJw7WxDsmLom92E7R_vu62kWISzl5pHneV56naV4yumGS6TeMS8F1LzZMb-RGCfaoOWVaiFYr2T-uc92398BJ8yznG0o7Okj-tDlhvRBaDuy0-X61mxEDKfsUsw9IfvoAGd8SICHe4kwKpB9YiIuJlAkT7HAt3hIfCqZbDMXHQKIjacJ1gRL9lkAqU_LF5-fNEwdzxhfH96z5dvHx-vxze_n105fzD5etFVyWtqNWSSa7raajQqeQWzmCU3yUTKihg7oTnUVhQXdas2GwgorR9UwN6EDws-b1oXeX4q8VczGLzxbnGQLGNRs1MKnryf8FO8p7rUVfQXYAbbWSEzqzS36BtDeMmnv15o96U2dpqvqaeXUsX8cFt38TR9cVeH8AfKg2F_gd07w1BfZzTC5BsD4b_lD_u3_iE8JcJgsJzU1cU6iGH_jdHV2npho</recordid><startdate>20080501</startdate><enddate>20080501</enddate><creator>Bajpai, Malini</creator><creator>Chopra, Puneet</creator><creator>Dastidar, Sunanda G</creator><creator>Ray, Abhijit</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20080501</creationdate><title>Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis</title><author>Bajpai, Malini ; Chopra, Puneet ; Dastidar, Sunanda G ; Ray, Abhijit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-20c65152d70b6ef6e3c5baf63b514692a15242ce4ca7277199c404bf8169efa43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antirheumatic Agents - adverse effects</topic><topic>Antirheumatic Agents - pharmacology</topic><topic>Antirheumatic Agents - therapeutic use</topic><topic>arthritis</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Arthritis, Rheumatoid - enzymology</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Clinical Trials as Topic</topic><topic>corticosteroid</topic><topic>Enzyme Inhibitors - adverse effects</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Humans</topic><topic>inflammation</topic><topic>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</topic><topic>kinase</topic><topic>Protein-Tyrosine Kinases - antagonists & inhibitors</topic><topic>Protein-Tyrosine Kinases - biosynthesis</topic><topic>R406</topic><topic>R788</topic><topic>Spleen - enzymology</topic><topic>Spleen - immunology</topic><topic>Syk</topic><topic>Syk Kinase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bajpai, Malini</creatorcontrib><creatorcontrib>Chopra, Puneet</creatorcontrib><creatorcontrib>Dastidar, Sunanda G</creatorcontrib><creatorcontrib>Ray, Abhijit</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Expert opinion on investigational drugs</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bajpai, Malini</au><au>Chopra, Puneet</au><au>Dastidar, Sunanda G</au><au>Ray, Abhijit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis</atitle><jtitle>Expert opinion on investigational drugs</jtitle><addtitle>Expert Opin Investig Drugs</addtitle><date>2008-05-01</date><risdate>2008</risdate><volume>17</volume><issue>5</issue><spage>641</spage><epage>659</epage><pages>641-659</pages><issn>1354-3784</issn><eissn>1744-7658</eissn><abstract>Background: In the last few years, significant progress has been made in understanding the pathogenic mechanisms and in defining the role of relevant cells and molecules in the pathophysiology of rheumatoid arthritis (RA). Various therapies, both biological (anti-TNF, anti-interleukins [e.g., IL-1]) and small molecule inhibitors have been explored for the treatment of RA. Objective: To date, no single signaling pathway inhibitor as wide acting as the corticosteroids, is known. However, treatment with corticosteroids is also associated with allied side effects. Despite a lot of efforts in the category of small molecule inhibitors, no inhibitor is available to deal with RA at both fronts (inflammation and tissue damage), without causing immense side effects. Method: This present review explores the role of spleen tyrosine kinase (Syk) in the pathogenesis of RA and also discusses how it may meet the present day therapeutic requirements for the treatment of RA. This review gives an in-depth discussion on the role of Syk signaling in RA, the possibilities of using Syk as a target and also discusses the possible side effects that could be associated with its inhibition. 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subjects | Animals Antirheumatic Agents - adverse effects Antirheumatic Agents - pharmacology Antirheumatic Agents - therapeutic use arthritis Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - enzymology Arthritis, Rheumatoid - immunology Clinical Trials as Topic corticosteroid Enzyme Inhibitors - adverse effects Enzyme Inhibitors - pharmacology Enzyme Inhibitors - therapeutic use Humans inflammation Intracellular Signaling Peptides and Proteins - antagonists & inhibitors kinase Protein-Tyrosine Kinases - antagonists & inhibitors Protein-Tyrosine Kinases - biosynthesis R406 R788 Spleen - enzymology Spleen - immunology Syk Syk Kinase |
title | Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis |
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