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    GENE:

    SYK (Spleen tyrosine kinase)

    i
    Other names: SYK, Spleen Associated Tyrosine Kinase, Spleen Tyrosine Kinase, Tyrosine-Protein Kinase SYK, P72-Syk
    12d
    Inhibition of autoantigen-induced B-cell receptor (BCR) internalization as a therapeutic strategy in diffuse large B cell lymphoma (DLBCL). (PubMed, Cell Death Dis)
    Finally, CME inhibition with dynamin-2 antagonists, such as phenothiazine derivatives, reduces BCR signaling, cell viability, and synergizes with SYK and PI3Kδ inhibitors. Since phenothiazines have well-defined safety and pharmacokinetic profiles, our data provide a framework for the rational design of clinical trials employing these drugs in the autoantigen-dependent subset of DLBCL.
    Journal
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    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • SYK (Spleen tyrosine kinase)
    13d
    Chemical synthesis of novel aminopyrimidin-4-yl-1H-pyrazole derivatives as spleen tyrosine kinase (SYK) inhibitors. (PubMed, Sci Rep)
    These integrative in silico and in vitro findings establish 44 as a promising lead molecule for SYK-targeted therapies, combining potent binding affinity, conformational stability, and effective enzyme inhibition. This work advances the design of novel small-molecule SYK inhibitors with potential applications in cancer and autoimmune disease treatment.
    Journal
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    SYK (Spleen tyrosine kinase)
    20d
    Paeoniflorin Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by SYK/SH3BP2 Signaling Pathway. (PubMed, Research (Wash D C))
    PF effectively attenuated hepatic metabolic dysregulation, inflammation, and fibrotic activation through inhibition of this pathway. Our work provided the first evidence establishing the SYK/SH3BP2 signaling axis as a pivotal pathway in MASLD progression, unveiling novel therapeutic targets while furnishing a mechanistic foundation for PF's potential application in MASLD treatment.
    Journal
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    PDGFRB (Platelet Derived Growth Factor Receptor Beta) • IL6 (Interleukin 6) • CD36 (thrombospondin receptor) • SYK (Spleen tyrosine kinase) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • CCL2 (Chemokine (C-C motif) ligand 2) • COL1A1 (Collagen Type I Alpha 1 Chain) • FASN (Fatty acid synthase) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • IL1B (Interleukin 1, beta) • NECTIN1 (Nectin Cell Adhesion Molecule 1) • PPARA (Peroxisome Proliferator Activated Receptor Alpha)
    1m
    Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function. (PubMed, Nat Immunol)
    Consequently, antigen-specific B cell generation and adaptive immune memory are disrupted, predisposing individuals to infection. Human CBL is critical for B cell development and function but redundant for T cell biology.
    Journal
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    SYK (Spleen tyrosine kinase)
    2ms
    The small-molecule Syk inhibitor R788 inhibits hematopoiesis and worsens anemia in sickle cell disease mice. (PubMed, Blood Vessel Thromb Hemost)
    Severe anemia and neutropenia induced by R788 in the sickle mouse model suggests that concomitant use of Syk inhibitors with hydroxyurea in patients with SCD should be approached cautiously. Further research is required to clarify the benefits and risks of selective Syk inhibition in SCD and other hemolytic conditions exhibiting stress hematopoiesis.
    Preclinical • Journal
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    TNFA (Tumor Necrosis Factor-Alpha) • SYK (Spleen tyrosine kinase)
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    hydroxyurea • Tavalisse (fostamatinib)
    2ms
    FcεRIγ Reinforces Double-Negative T cell-mediated Antibody-dependent Cellular Cytotoxicity Against Tumor Cells. (PubMed, J Mol Cell Biol)
    Binding of IgG1 to FcεRIγ activates the FcεRIγ/Syk/AKT/NF-κB pathway, consequently enhancing tumor cell killing. Thus, DNT cells may play a significant role in cancer immunity, providing a basis for novel immune cell and antibody combination therapies.
    Journal
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    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • SYK (Spleen tyrosine kinase) • FCER1G (Fc Fragment Of IgE Receptor Ig)
    2ms
    Dissecting CAF Heterogeneity in Glioblastoma Reveals Prognostic Subtypes and a Central Regulatory Role for Spleen Tyrosine Kinase (SYK). (PubMed, Cancers (Basel))
    Our study reveals CAF subtype-associated patterns with prognostic and functional relevance in GBM. Targeting CAF subpopulations and key mediators such as SYK may represent a promising therapeutic strategy in GBM.
    Journal
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    SYK (Spleen tyrosine kinase)
    2ms
    TIPE2 deficiency enhances macrophage phagocytosis of tumor cells. (PubMed, J Immunother Cancer)
    TIPE2 represents a negative regulatory mechanism for macrophage phagocytosis against tumor cells. In the future, TIPE2 may serve as a promising target to enhance the efficacy of tumor immunotherapy strategies based on macrophages.
    Journal
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    SYK (Spleen tyrosine kinase)
    2ms
    Whole glucan particles enhance immune modulation in combination with TIGIT checkpoint blockade through Dectin-1 activation. (PubMed, Int J Biol Macromol)
    While the detailed signaling and apoptosis analyses were performed in LLC, the 4 T1 cohort reproduced the antitumor efficacy and immune-activation signatures, supporting generalizability. These results indicated that WGP augments TIGIT blockade through Dectin-1 mediated myeloid reprogramming and coordinated innate adaptive activation, and they supported β-glucan based innate priming as a rational partner for TIGIT and potentially other T-cell-directed checkpoint inhibitors.
    Journal • Checkpoint inhibition
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    CD8 (cluster of differentiation 8) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • IL10 (Interleukin 10) • SYK (Spleen tyrosine kinase) • TGFB1 (Transforming Growth Factor Beta 1) • CLEC7A (C-Type Lectin Domain Containing 7A)
    2ms
    Recent Progress of Molecular Design and Activities of Spleen Tyrosine Kinase (SYK) Inhibitors. (PubMed, Drug Dev Res)
    This article comprehensively reviews recent advances in SYK inhibitor research, focusing on their therapeutic potential in autoimmune diseases and hematologic cancers. Furthermore, we highlight representative SYK inhibitors, discuss their clinical applications, outline current challenges, and future directions in this evolving field.
    Review • Journal
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    SYK (Spleen tyrosine kinase)
    2ms
    Fostamatinib (R788), a spleen tyrosine kinase inhibitor, sensitizes pancreatic cancer cells to oncolytic vesicular stomatitis virus. (PubMed, Mol Ther Oncol)
    Additionally, fostamatinib inhibited PDAC cell proliferation even in the absence of viral infection, while ruxolitinib did not. Our data suggest that fostamatinib may be repurposed as an effective drug that enhances OV therapy in PDAC by promoting OV replication and suppressing tumor growth.
    Journal
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    SYK (Spleen tyrosine kinase)
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    Jakafi (ruxolitinib) • Tavalisse (fostamatinib)
    2ms
    FcεRγI promotes canine CD8 chimeric antigen receptor T cell cytotoxicity through a Syk-NFκB axis. (PubMed, Mol Ther)
    Syk-NFκB signaling promotes FcεRγI expression in hBBζ CARTs, and CAR-TCR interactions potentiate NFκB signaling to upregulate FcεRγI and enhance CART function. These studies identify a potent therapeutic subset of innate-like canine CARTs induced by hBBζ signaling, which holds potential to improve both canine and human CART therapy.
    Journal • IO biomarker
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    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • SYK (Spleen tyrosine kinase) • GZMB (Granzyme B) • FCER1G (Fc Fragment Of IgE Receptor Ig)
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    CD20 negative