Table 1 In vitro and in vivo pre-clinical evidence in support of the therapeutic potential of GSK-J4 in various diseases

Malignancies

Acute myeloid leukaemia (AML)

GSK-J4 reduces proliferation and colony-forming ability of primary AML cells and AML cell lines

GSK-J4 displays anti-tumour activity in AML xenograft mouse model

[24]

GSK-J4 dose-dependently induces cell cycle arrest in the S phase in AML cell lines

[92]

T cell acute lymphoblastic leukaemia (T-ALL)

GSK-J4 suppresses the growth of T-ALL cell lines and primary T-ALL cells by inducing cell cycle arrest and apoptosis

–

[28]

Colorectal cancer

GSK-J4 sensitises colorectal cancer cells to oxaliplatin-induced apoptosis

GSK-J4 reduces tumour volume in mice injected with oxaliplatin-resistant patient-derived xenografts

[34]

GSK-J4 sensitises colorectal cancer cells to fluorouracil

Prostate cancer

GSK-J4 inhibits proliferation of castration-resistant prostate cancer cell lines

–

[37]

GSK-J4 sensitises castration-resistant prostate cancer cell lines to cabazitaxel

Breast cancer

GSK-J4 inhibits the self-renewal capacity and colony-forming ability of breast cancer stem cells

GSK-J4 suppresses tumour growth in breast cancer xenograft mouse model

[39]

GSK-J4 sensitises luminal breast cancer cell lines to phosphoinositide 3-kinase inhibitors

[41]

Neuroblastoma

GSK-J4 reduces viability in neuroblastoma cell lines

GSK-J4 blocks growth of chemorefractory and patient-derived xenografts in mice

[31]

Gliomas

GSK-J4 inhibits proliferation of native and temozolomide-resistant glioblastoma cells by blocking cell cycle progression into G2 phase

GSK-J4 improves survival in mice with H3K27 mutation-harbouring diffuse intrinsic pontine glioma xenografts

[50]

Inflammatory conditions

Rheumatoid arthritis (RA)

GSK-J4 inhibits PDGFBB-induced proliferation and migration of fibroblast-liked cnidocytes

GSK-J4 ameliorates joint swelling and bone erosion and destruction in mouse model of collagen-induced arthritis

[60]

GSK-J4 inhibits IFNγ production in natural killer cells derived from peripheral bloods and synovial fluids of patients with RA

[53]

GSK-J4 inhibits the ability of NK cells to promote the formation of osteoclasts, which mediate bone erosion in RA

[53]

GSK-J4 inhibits TNFα production in macrophages from patients with RA

[18]

Osteoarthritis

GSK-J4 disrupts collagen (COL2A1 and COL10A1) and glycosaminoglycan (aggrecan) synthesis in chondrogenic mesenchymal stem cells

GSK-J4 protects against cartilage erosion in destabilisation of medial meniscus (DMM) murine model of osteoarthritis

[63]

GSK-J4 inhibits the expression of cartilage destroying proteases MMP9, MMP13 and ADAMTS5 in human articular chondrocytes

[63]

Inflammatory bowel disease

GSK-J4 promotes tolerogenic capacity of dendritic cells in vitro

GSK-J4 ameliorates severity of dextran sodium sulphate (DSS)-induced colitis in mice

[68]

Dendritic cell treated ex vivo with GSK-J4 attenuates DSS-induced colitis in mice by promoting CD4⁺ T cell polarisation towards Treg rather than Th17

Atherosclerosis

GSK-J4 inhibits PDGFBB-induced proliferation and migration of aortic smooth muscle cells

GSK-J4 attenuates neointimal formation in mice with carotid artery ligation

[71]

Multiple sclerosis

–

GSK-J4 reduces severity of experimental autoimmune encephalomyelitis in mice

[56]

Pathogens

Schistosomiasis

GSK-J4 dose-dependently reduces motility and viability of adult schistosomal worms and drug-resistant schistosomula

–

[91]

Respiratory syncytial virus (RSV)

GSK-J4 inhibits antigen-presenting capacity of bone marrow-derived and pulmonary dendritic cells infected with RSV

GSK-J4 ameliorates pulmonary immunopathology associated with RSV infection in mice

[77]

Herpes simplex virus 1 (HSV1)

GSK-J4 inhibits induced reactivation of HSV1 from latency in primary adult murine trigeminal ganglion neurons

–

[85]

Human immunodeficiency virus 1 (HIV1)

GSK-J4 inhibits induced reactivation of HIV1 from latency in T cells

–

[82]

Escherichia coli (E. coli)

GSK-J4 inhibits LPS-induced expression of pro-inflammatory cytokines in macrophages derived from the peritoneum of septic mice infected with E. coli

GSK-J4 protects against early sepsis and improves survival in mice injected with E. coli strains from human clinical specimens

[88]