ACR Meeting Abstracts

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Abstracts tagged "kinase"

  • Abstract Number: 2771 • 2017 ACR/ARHP Annual Meeting

    NOMID-Associated Complications in Mice Are Prevented By CDD-450, a Small Molecule Inhibitor of the Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) Pathway

    Gabriel Mbalaviele1, Chun Wang1, Susan Hockerman2, Jon Jacobsen2, Jeff Hirsch2, Steve Mnich2, Heidi Hope2, Matt Saabye2, Hal Hoffman3 and Joseph Monahan2, 1Medicine, Washington University School of Medicine,, St. Louis, MO, 2Confluence Life Sciences, Inc, St. Louis, MO, 3University of California, San Diego, San Diego, CA

    Background/Purpose: NLRP3-activating mutations cause cryopyrinopathies of which NOMID is the most severe phenotype. NLRP3 assembles a protein complex, responsible for the maturation of IL-1β and…
  • Abstract Number: 514 • 2017 ACR/ARHP Annual Meeting

    BMS-986195, a Novel, Rapidly Acting, Covalent Inhibitor of Bruton’s Tyrosine Kinase: Safety, Pharmacokinetic and Pharmacodynamic Profiles in Healthy Participants

    IM Catlett, L Wei, N Zheng, A Liu, B He, I Girgis and M Nowak, Bristol-Myers Squibb, Princeton, NJ

    Background/Purpose: Bruton’s tyrosine kinase (BTK) is an attractive, novel therapeutic target for autoimmune disease, as it is required for signal transduction and activation via B-cell…
  • Abstract Number: 1320 • 2017 ACR/ARHP Annual Meeting

    TAS5315, a Novel Bruton’s Tyrosine Kinase Inhibitor, Ameliorates Inflammation and Bone Erosion in Murine Model for Rheumatoid Arthritis

    Yohei Yoshiga1, Fumihito Hosoi1, Satoru Iguchi1, Ryuusuke Kaneko2, Yoshinori Nakachi1, Daichi Akasaka2, Kenji Tanaka2, Kazuhiko Yonekura2, Teruhiro Utsugi2, Eiji Sasaki2 and Yoshikazu Iwasawa2, 1TAIHO PHARMACEUTICAL CO., LTD., TSUKUBA, Japan, 2TAIHO PHARMACEUTICAL CO., LTD., Tsukuba, Japan

    Background/Purpose: The erosions of bone and cartilage are a cardinal feature of rheumatoid arthritis (RA) and associated with disease severity and poor functional outcome. Although…
  • Abstract Number: 1567 • 2017 ACR/ARHP Annual Meeting

    A Mitogen-Associated Protein Kinase (MAPK) Associated Kinase 2 Inhibitor Decreases in Vitro Th17 and Monocyte Inflammatory Responses in Spondyloarthritis

    Davide Simone, Hui Shi, Nuha Ansar, Alison Davies, Karen Doig and Paul Bowness, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom

    Background/Purpose: The current biologic treatment for Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA) are limited to TNF-a inhibitors (TNFi) and, more recently, IL-17A monoclonal antibodies.…
  • Abstract Number: 460 • 2016 ACR/ARHP Annual Meeting

    TAS5315, a Novel Bruton’s Tyrosine Kinase Inhibitor, Demonstrates Anti-Inflammatory Effect in Autoimmune Disease Models

    Yohei Yoshiga1, Fumihito Hosoi1, Satoru Iguchi1, Ryuusuke Kaneko1, Yoshinori Nakachi1, Daichi Akasaka1, Kenji Tanaka2, Kazuhiko Yonekura2, Teruhiro Utsugi2, Eiji Sasaki2 and Yoshikazu Iwasawa2, 1TAIHO PHARMACEUTICAL CO., LTD., TSUKUBA, Japan, 2TAIHO PHARMACEUTICAL CO., LTD., Tsukuba, Japan

    Background/Purpose:  Bruton’s Tyrosine Kinase (BTK), a non-receptor tyrosine kinase is involved in intracellular signaling pathways downstream of several receptors, including the B cell receptor (BCR),…
  • Abstract Number: 1436 • 2016 ACR/ARHP Annual Meeting

    TAS8274, a Highly Selective Janus Kinase 3 Inhibitor, Demonstrates Potent Efficacy in an Animal Model of Rheumatoid Arthritis

    Hiroaki Hayashi, Takafumi Harada, Shunsuke Demizu, Fumito Tatsuzawa, Ken Sato, Morihiro Mitsuya, Kenji Tanaka, Kazuhiko Yonekura, Teruhiro Utsugi, Eiji Sasaki and Yoshikazu Iwasawa, TAIHO PHARMACEUTICAL CO., LTD., Tsukuba, Japan

    Background/Purpose:   The family of Janus kinases (JAKs) plays important roles in signaling pathway mediated by various cytokine receptors. An aberrant activation of JAK-STAT signaling…
  • Abstract Number: 2166 • 2014 ACR/ARHP Annual Meeting

    Bim Suppresses the Development of Glomerulonephritis By Inhibiting M2 Polarization

    Fu-Nien Tsai, Northwestern University, Chicago, IL

    Background/Purpose Only recently have monocytes and macrophages been accepted as critical players in the pathogenesis of SLE.  However, very little is known regarding the molecular…
  • Abstract Number: 1500 • 2014 ACR/ARHP Annual Meeting

    Preclinical and Clinical Characterization of MK-8457, a Selective Spleen Tyrosine Kinase and Zeta-Chain-Associated Protein Kinase 70 Inhibitor, in Normotensive and Hypertensive Cardiovascular Models

    Hani Houshyar1, Alan Bass2, Judith Boice3, Michael Ellis4, Patrick Fanelli5, Tomoko Freshwater6, Jane Guo7, Kimberly Hoagland5, Janet Kerr5, Alan Northrup4, Mathew Maddess8, Richard Miller9, Marcella Ruddy10, Stella Vincent11, Jayanthi Wolf5, Haoling Weng3, Gloria Zingaro5 and Gene Marcantonio3, 133 Avenue Louis Pasteur, Merck & Co., Boston, MA, 2Safety Assessment, Merck & Co., Boston, MA, 3Merck & Co., Whitehouse Station, NJ, 4Medicinal Chemistry, Merck & Co., Boston, MA, 5Merck & Co., West Point, PA, 6PPDM Early Stage, Merck & Co., Rahway, NJ, 7Immunology, Merck & Co., Boston, MA, 8Discovery Process Chemistry, Merck & Co., Boston, MA, 9Biochemistry & Biophysics, Merck & Co., Boston, MA, 10Merck & Co., Boston, MA, 11PPDM Preclinical ADME, Merck & Co., Boston, MA

    Background/Purpose:  Spleen Tyrosine Kinase (SYK) and Zeta-chain-associated protein kinase 70 (ZAP70) are non-receptor protein kinases that bind phosophorylated receptor tyrosine-based activation motifs, critical in immune…
  • Abstract Number: 267 • 2014 ACR/ARHP Annual Meeting

    Selective and Peripheral-Specific Trk Inhibitor Shows Potent Analgesic Effect Comparable to Morphine in Rat Osteoarthritis Model without CNS Toxicity

    Takeshi Nagaura1, Tetsuya Yasuhiro2, Keisuke Oda2, Yuya Ezaki2, Takashi Koyanagi2, Satoshi Itadani2, Hiroyuki Nitta2, Hiroshi Wakazono2, Seishi Katsumata2 and Yasushi Hirota2, 1Discovery Research Laboratories I, Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd., Osaka, Japan, 2Ono Pharmaceutical Co., Ltd., Osaka, Japan

    Background/Purpose Tropomyosin receptor kinase (Trk) receptors are a family of three closely related receptor tyrosine kinases; TrkA, TrkB and TrkC. Especially, the peripheral TrkA in…
  • Abstract Number: 2562 • 2013 ACR/ARHP Annual Meeting

    Inhibition Of SOX9 Phosphorylation Abrogates The Increased Expression Of Profibrotic Genes In Systemic Sclerosis Dermal Fibroblasts

    Sonsoles Piera-Velazquez, Alma Makul and Sergio A. Jimenez, Jefferson Institute of Molecular Medicine, Division of Connective Tissue Diseases and Scleroderma Center,Thomas Jefferson University, Philadelphia, PA

    Background/Purpose: SOX9, a high mobility group transcription factor is a master regulator of chondrogenesis and plays a crucial role in the regulation of chondrocyte gene…
  • Abstract Number: 2525 • 2012 ACR/ARHP Annual Meeting

    Bruton’s Tyrosine Kinase Inhibition Suppresses Inflammatory Cytokine Production and Affects Gene Expression in Human Macrophages and RA Synovial Tissue Explants

    Linda M. Hartkamp1, Inge E. van Es1, Jay S. Fine2, Michael Smith2, John Woods2, Satwant Narula3, Julie DeMartino2, Paul P. Tak4 and Kris A. Reedquist1, 1Department of Experimental Immunology, Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, 2Inflammation Discovery, Hoffmann-La Roche, Nutley, NJ, 3Inflammatory Discovery, Hoffmann-La Roche, Nutley, NJ, 4Division of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam and GlaxoSmithKline, Amsterdam, Netherlands

    Background/Purpose: Rheumatoid arthritis (RA) is a chronic and progressive autoinflammatory disorder characterized by the infiltration of inflammatory cells, including B-cells, T-cells and macrophages, in the…
  • Abstract Number: 2332 • 2012 ACR/ARHP Annual Meeting

    Suppression of PP2Ac Causes DNA Hypermethylation Through Enhanced Pmek/Perk Activity in T Cells

    Katsue S. Watanabe1, Kamalpreet Nagpal2 and George C. Tsokos3, 1Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan, 2Medicine/Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 3Medicine/Rheumatology, BIDMC, Harvard Medical School, Boston, MA

    Background/Purpose: Although many reports have focused on the impaired MEK-ERK signaling pathway in T cells from systemic lupus erythematosus (SLE) patients which results in suppression…
  • Abstract Number: 1799 • 2012 ACR/ARHP Annual Meeting

    ONO-4059 – A Novel Small Molecule Bruton’s Tyrosine Kinase (Btk) Inhibitor, Suppresses Osteoclast Differentiation and Activation

    Yuko Ariza, Toshio Yoshizawa, Yoshiko Ueda, Shingo Hotta, Masami Narita and Kazuhito Kawabata, Discovery Research Laboratories 3, Ono Pharmaceutical Co., Ltd., Osaka, Japan

    Background/Purpose:  Bruton’s tyrosine kinase (Btk) is primarily expressed in B cells, mast cells, platelets, myeloid cells and osteoclasts. Osteoclast differentiation is regulated by signaling pathways…
  • Abstract Number: 1741 • 2012 ACR/ARHP Annual Meeting

    Suppression of Glomerulonephritis in NZB/W F1 Mice by a Selective Inhibitor of Bruton’s Tyrosine Kinase (RN486)

    Paola Mina-Osorio1, Jacob LaStant1, Natalie Keirstead1, Toni Whittard1, Stella Stefanova1, Alka Patel1, Jennifer Postelnek1, John Woods2, Soo Min2, Yong Kim1, Julie Demartino2, Satwant Narula3 and Daigen Xu1, 1Inflammation, Hoffmann-La Roche, Nutley, NJ, 2Inflammation Discovery, Hoffmann-La Roche, Nutley, NJ, 3Inflammatory Discovery, Hoffmann-La Roche, Nutley, NJ

    Background/Purpose: Bruton tyrosine kinase (Btk) is a Tec family kinase that participates in B cell receptor (BCR), Toll-like Receptor (TLR) and chemokine receptor signaling. It…
  • Abstract Number: 880 • 2012 ACR/ARHP Annual Meeting

    Interferon Regulatory Factor 8 Regulates BAFF Production in Murine Macrophages and Is a Nexus for Cross Talk Between IFN-γ and TGF-β

    Weijia Yuan1, Sanjay Gupta2, Jane E. Salmon3 and Alessandra B. Pernis2, 1Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, 2Autoimmunity & Inflammation, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, 3Dept of Medicine, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY

    Background/Purpose: Lupus is a systemic autoimmune disease that can lead to severe end-organ damage characterized by unabated inflammation and aberrant tissue repair. Macrophage dysregulation plays…
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