Copyright
©The Author(s) 2020.
World J Gastroenterol. Mar 14, 2020; 26(10): 1005-1019
Published online Mar 14, 2020. doi: 10.3748/wjg.v26.i10.1005
Published online Mar 14, 2020. doi: 10.3748/wjg.v26.i10.1005
Compound | Medical condition | Description/effect | Ref. |
Fostamatinib (R788) | Ulcerative colitis | Suppression of TNFα, T cells and neutrophils | [106] |
Rheumatoid arthritis | Reduced inflammation and tissue damage, suppressed clinical arthritis, pannus formation and synovitis | [107,108] | |
Chronic lymphocytic leukemia and Non-Hodgkin lymphoma | Disruption of BCR signaling inhibiting the proliferation and survival of malignant B cells | [109,110] | |
Ischemia-reperfusion induced intestinal and lung damage | Impaired release of pro-inflammatory and coagulation mediators, reduced neutrophils, macrophages and platelet accumulations | [111] | |
Glomerulonephritis | Reduced proteinuria, glomerular macrophage and CD8 cells, MCP-1 and IL-1β, and renal injury | [112] | |
Entospletinib (GS-9973) | Chronic lymphocytic leukemia | Decreased inflammation and disruption of chemokine/cytokine circuits (BCR signaling) | [113-115] |
Diffuse large B-cell lymphoma | Disruption of BCR signaling inhibiting the proliferation and survival of malignant B cells | [116] | |
Cherubisme (craniofacial disorder) | Ameliorates inflammation and bone destruction in the mouse model of cherubism | [117] | |
Cerdulatinib (PRT062070) | Diffuse large B-cell lymphoma | Disruption of BCR signalling inhibiting the proliferation and survival of malignant B cells | [118,119] |
TAK-659 | Epstein-Barr virus-associated lymphoma | Inhibited tumour development and metastases | [120] |
Chronic lymphocytic leukemia | Decreased tumour survival, myeloid cell proliferation and metastasis | [121] | |
R406 (tamatinib) | Immunocomplexes mediated inflammation | Inhibits several critical modes of the inflammatory cascade | [122] |
Human platelets | Inhibition of activation of CLEC-2 (C-type lectin 2, platelet receptor), and platelet activation | [123] | |
Chronic lymphocytic leukemia | Inhibition of constitutive and BCR-induced SYK activation, abrogation of CLL cell survival, migration, and paracrine signalling | [124] | |
Leukemia | Reduced tyrosine phosphorylation and c-Myc expression, blockade of tumorigenic cells proliferation transformed by oncogenes | [125] | |
Megakaryocytic leukemia | Induced apoptosis, reduced cell proliferation and blockade of STAT5 signalling | [126] | |
Glomerulonephritis | Downregulated MCP-1 production from mesangial cells and macrophages | [112] | |
Piceatannol | Oral squamous cell carcinoma | Inhibited tumour cell proliferation, induced of apoptosis, attenuated VEGF and MMP9 expression, and decreased metastases | [127] |
Inhibitor | Mechanism of action | Therapeutic effect | Ref. |
R406 | Blocking of Fc receptor signalling pathway, NF-κB signalling pathway and inflammasome activation | Reduced SYK expression and phosphorylation resulting in attenuated liver steatosis, inflammation and fibrosis in ASH and NASH murine models | [20,44] |
GS-9973 | Decreased expression of HSCs activation (CBP, MYB, MYC) and HSCs proliferation factors (MYC and CCND1) | Inhibition of HSCs proliferation and HSC activation resulting in amelioration of fibrosis and hepatocarcinogenesis | [28] |
PRT062607 and piceatannol | Increased intra-tumoral p16, p53 and decreased expression of Bcl-xL and SMAD4. Decreased expression of genes regulating angiogenesis, apoptosis, cell cycle regulation and cellular senescence. Down-regulation of mTOR, IL-8 signalling and oxidative phosphorylation | Reduced HSCs differentiation and infiltration of inflammatory cells including T cells, B cells and myeloid cells, reduced oncogenic progression. Marked attenuation of toxin-induced liver fibrosis, associated hepatocellular injury, intra-hepatic inflammation and hepatocarcinogenesis | [128] |
- Citation: Kurniawan DW, Storm G, Prakash J, Bansal R. Role of spleen tyrosine kinase in liver diseases. World J Gastroenterol 2020; 26(10): 1005-1019
- URL: https://www.wjgnet.com/1007-9327/full/v26/i10/1005.htm
- DOI: https://dx.doi.org/10.3748/wjg.v26.i10.1005