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    DRUG CLASS:

    IKKe inhibitor

    Related drugs:
    3d
    A novel functional IKBKE variant activating NFAT in a patient with polyarthritis and a remittent fever. (PubMed, Front Immunol)
    She had a poor response to corticosteroids or disease-modifying antirheumatic drugs, including the tumor necrosis factor-α antagonist, etanercept, and the anti-interleukin-6 receptor antibody, tocilizumab. A novel functional heterozygous variant in IKBKE is described in a patient with a remittent fever and arthritis. The data suggest that IKBKE is an important negative regulator of inflammation, particularly in T cells, and this IKBKE variant might be the underlying cause of a novel autoinflammatory pathology.
    Journal
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    CD4 (CD4 Molecule) • IL6R (Interleukin 6 receptor) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
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    Actemra IV (tocilizumab)
    3ms
    BMS345541 is predicted as a repurposed drug for the treatment of TMZ-resistant Glioblastoma using target gene expression and virtual drug screening. (PubMed, Cancer Genet)
    Glioblastoma (GBM) is one of the most aggressive and fatal cancers, for which Temozolomide (TMZ) chemo drug is commonly used for its treatment. The ADMET analysis of this drug BMS345541 shows a higher half-life and lower cytotoxicity level than other predicted repurposed drugs. Hence, we conjecture that this could be a better drug for increasing the sensitivity of TMZ for treating GBM patients.
    Journal
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    FOXG1 (Forkhead Box G1)
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    temozolomide • BMS-345541
    4ms
    Exploring the Roles of Key Mediators IKBKE and HSPA1A in Alzheimer's Disease and Hepatocellular Carcinoma through Bioinformatics Analysis. (PubMed, Int J Mol Sci)
    Our study indicates that IKBKE and HSPA1A could influence the onset and progression of AD and LIHC by modulating the infiltration levels of immune cells. This lays a foundation for future research into targeted therapies based on their shared mechanisms.
    Journal
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    HSPA1A (Heat Shock Protein Family A (Hsp70) Member 1A) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    5ms
    The impact of MCCK1, an inhibitor of IKBKE kinase, on acute B lymphocyte leukemia cells. (PubMed, Math Biosci Eng)
    In vivo experiments using B-ALL mouse tumor models substantiated MCCK1's efficacy in impeding tumor proliferation. These findings collectively suggest that IKBKE, found to be elevated in B-ALL patients, may serve as a promising drug target, with MCCK1 demonstrating potential for inducing apoptosis in B-ALL cells both in vitro and in vivo.
    Journal
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    IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    5ms
    Prognostic implication and immunotherapy response prediction of a novel ubiquitination-related gene signature in liver cancer. (PubMed, Aging (Albany NY))
    In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC.
    Journal • Gene Signature • IO biomarker
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    MCM10 (Minichromosome Maintenance 10 Replication Initiation Factor)
    |
    erlotinib • bortezomib • VTX-11e • BMS-345541 • AT7519
    9ms
    Atypical inflammatory kinase IKBKE phosphorylates and inactivates FoxA1 to promote liver tumorigenesis. (PubMed, Sci Adv)
    Notably, Ikbke knockout delays diethylnitrosamine (DEN)-induced mouse liver tumor development. Together, our findings not only reveal FoxA1 as a bona fide substrate and negative nuclear effector of IKBKE in hepatocellular carcinioma (HCC) but also provide a promising strategy to target IKBEK for HCC therapy.
    Journal
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    FOXA1 (Forkhead Box A1) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    10ms
    Low CDKN1B Expression Associated with Reduced CD8+ T Lymphocytes Predicts Poor Outcome in Breast Cancer in a Machine Learning Analysis. (PubMed, J Pers Med)
    In in vitro drug screening, BMS-345541 demonstrated efficacy as a therapeutic targeting of CDKN1B, effectively impeding the growth of breast cancer cells characterized by low CDKN1B expression. The inclusion of CDKN1B expression in GBM models increased the accuracy of survival predictions. CDKN1B expression plays a significant role in breast cancer progression, implying that targeting CDKN1B might be a promising strategy for treating breast cancer.
    Journal • IO biomarker • Machine learning
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    CD8 (cluster of differentiation 8) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CDKN1B (Cyclin dependent kinase inhibitor 1B)
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    CDKN1B expression
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    BMS-345541
    10ms
    IKBKE promotes the ZEB2-mediated EMT process by phosphorylating HMGA1a in glioblastoma. (PubMed, Cell Signal)
    Hence, HMGA1a affects ZEB2 expression and promotes ZEB2-related metastasis process. Consequently, IKBKE exerts oncogenic functions via the IKBKE/HMGA1a/ZEB2 axis, and IKBKE may be a prominent biomarker for the treatment of glioblastoma in the future.
    Journal
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    HMGA1 (High Mobility Group AT-Hook 1) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • ZEB2 (Zinc Finger E-Box Binding Homeobox 2)
    11ms
    Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation. (PubMed, J Pharm Anal)
    Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/β ratio and restored irradiation-induced downregulation of p62 expression...In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.
    Journal
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    CDK4 (Cyclin-dependent kinase 4) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    1year
    Ginsenoside Rg5's Enhancement of Radiosensitivity of Lung Adenocarcinoma via Reducing HSP90 CDC37 Interaction and Promoting Client Protein Degradation. (PubMed, Int J Radiat Oncol Biol Phys)
    ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90 and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.
    Journal
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    CDK4 (Cyclin-dependent kinase 4) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    1year
    IKBKE Promotes Radioresistance of Glioblastoma through AKT/FOXO3a Pathway. (PubMed, Int J Radiat Oncol Biol Phys)
    IKBKE can activate AKT independent of PI3K by directly phosphorylating AKT Ser473 and Thr308, thus increasing the phosphorylation of FOXO3a. Phosphorylated FOXO3a promoted its ubiquitin degradation, and inhibited its transportation into the nucleus, causing radioresistance in glioblastoma. IKBKE inhibitor Amlexanox can pass through the blood-brain barrier and increase the radiosensitivity of intracranial tumor cells.
    Journal
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    IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • H2AX (H2A.X Variant Histone)
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    Aphthasol (amlexanox) • MG132
    1year
    IKBKE regulates angiogenesis by modulating VEGF expression and secretion in glioblastoma. (PubMed, Tissue Cell)
    This study reveals that IKBKE is a novel oncogenic molecule that induces angiogenesis through the promotion of VEGF expression and highlights the potential of targeting IKBKE for glioblastoma therapy.
    Journal
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    VEGFA (Vascular endothelial growth factor A) • FOXO3 (Forkhead box O3) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
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    VEGFA expression
    over1year
    NF-ΚB AND JAK/STAT PATHWAYS INHIBITION REVERSES FIBROSIS IN A MURINE MODEL OF INFLAMMATION-DRIVEN MYELOFIBROSIS (EHA 2023)
    Aims: To assess whether inhibition of NF-κB and/or JAK/STAT signaling can attenuate the inflammatory state and reverse the MF-like phenotype in an aged miR-146a -/- mouse model, using either (a) the JAK1/2 inhibitor ruxolitinib (RUX), (b) the NF-κB pathway inhibitor, through IKKα/β, BMS-345541 (BMS), (c) RUX+BMS, or (d) the dual JAK2/IRAK1 inhibitor pacritinib (PAC). In an aging-associated MF-like murine model without driver mutations, NF-κB inhibitors, either alone or incombination with JAK inhibitors, as well as dual-acting inhibitors, reduced inflammatory cytokines and splenomegaly, reversed thrombocytopenia and improved BM fibrosis. The combination therapy (RUX+BMS) produced BM aplasia and worsened anemia, whereas the dual inhibitor (PAC) improved or stabilized hematologic parameters. Bone Marrow Fibrosis, Myelofibrosis, NF- B, Myeloproliferative disorder
    Preclinical
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    IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • ITGAM (Integrin, alpha M) • IL1B (Interleukin 1, beta) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1) • TRAF6 (TNF Receptor Associated Factor 6)
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    JAK2 V617F
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    Jakafi (ruxolitinib) • Vonjo (pacritinib) • BMS-345541
    almost2years
    Molecular characterization of advanced primary cardiac sarcomas (Sarcoma-RC 2023)
    All patients gained clinical benefit by first-line doxorubicin-based chemotherapy (2 partial responses, 2 stable disease), although disease control was short-lived (<10 months)...The somatic NGS analysis was consistent with the genomic profile of soft tissue sarcomas and cfDNA analysis was demonstrated for the first time in this rare tumor type to be a potential tool for dynamic tracking of clinical outcome. Legal entity responsible for the study The authors.
    Tumor mutational burden • BRCA Biomarker • Metastases
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor) • MTAP (Methylthioadenosine Phosphorylase) • MDM2 (E3 ubiquitin protein ligase) • KMT2D (Lysine Methyltransferase 2D) • PTCH1 (Patched 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TSC2 (TSC complex subunit 2) • NOTCH2 (Notch 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • NOTCH3 (Notch Receptor 3) • EP300 (E1A binding protein p300) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • IRS2 (Insulin receptor substrate 2) • MAPK1 (Mitogen-activated protein kinase 1) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • CCND3 (Cyclin D3) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • CTNNA1 (Catenin Alpha 1) • EPHB4 (EPH receptor B4) • RAD52 (RAD52 Homolog DNA Repair Protein) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • ALOX12B (Arachidonate 12-Lipoxygenase) • FANCC (FA Complementation Group C) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
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    TMB-L • MDM2 amplification • RET mutation • MET mutation • PTCH1 mutation • FANCA mutation • TSC2 mutation • TP53 R196*
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    FoundationOne® CDx
    |
    doxorubicin hydrochloride
    2years
    Phosphoproteomics of extracellular vesicles integrated with multiomics analysis reveals novel kinase networks for lung cancer. (PubMed, Mol Carcinog)
    Key phosphoproteins of network nodes were validated in patients' EVs, including MAPK6 , IKBKE , SRC , CDK7 , and CDK1 . These networks depict intrinsic signal-regulation derived from EVs' phosphoproteins, providing a comprehensive and pathway-based strategy for in-depth lung cancer research.
    Journal
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    CDK7 (Cyclin Dependent Kinase 7) • CDK1 (Cyclin-dependent kinase 1) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    2years
    Dual Inhibition of NF-Kb and JAK/STAT Pathways Reverts Myelofibrosis-like Phenotype in an In Vivo Murine Model (ASH 2022)
    11-month-old miR-146a-/- mice were 1-month-oral ad libitum treated with either ruxolitinib (JAK1/2 inhibitor) at 75 mg/kg/day, BMS-345541 (BMS) (NF-κB pathway inhibitor at IKKα/β level) at 100 mg/kg/day, both inhibitors at the same concentrations, or pacritinib (JAK2 and NF-κB pathway inhibitor at IRAK1 level) at 150 mg/kg/day. miR-146a-/- mice constitute a useful model of MPN without driver mutations to evaluate the role of inflammation in these neoplasms. The dual inhibition of NF-κB and JAK/STAT with pacritinib reduced inflammatory cytokines, reverted monocytopenia and thrombocytopenia, and improved BM fibrosis without worsening anemia. While some of these benefits could be recapitulated in vivo by combining ruxolitinib with an NF-κB inhibitor, this combination resulted in worsening anemia and BM aplasia.
    Preclinical
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    CD19 (CD19 Molecule) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • ITGAM (Integrin, alpha M) • IL1B (Interleukin 1, beta) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1) • RELA (RELA Proto-Oncogene) • TRAF6 (TNF Receptor Associated Factor 6)
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    JAK2 V617F
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    Jakafi (ruxolitinib) • Vonjo (pacritinib) • BMS-345541
    2years
    Pan-Cancer Analysis on the Oncogenic Role of Programmed Cell Death 10. (PubMed, J Oncol)
    The results of our investigation demonstrate that PDCD10 has an oncogenic function in many cancer types. This study provides a reference for future research on antitumor therapeutic targets.
    Journal • IO biomarker • Pan tumor
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    FGFR1 (Fibroblast growth factor receptor 1) • IFNG (Interferon, gamma) • STRN (Striatin) • AURKB (Aurora Kinase B) • FGFR1OP2 (FGFR1 Oncogene Partner 2) • TGFB1 (Transforming Growth Factor Beta 1) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • PPM1A (Protein Phosphatase Mg2+/Mn2+ Dependent 1A) • PPP2CA (Protein Phosphatase 2 Catalytic Subunit Alpha 2) • STK25 (Serine/Threonine Kinase 25)
    2years
    Ocular adnexal lymphoma: Subtype-specific clinical and genetic features. (PubMed, Acta Ophthalmol)
    Alt i alt viser resultaterne, at den histologiske undertype er en vigtig prognostisk faktor for lymfomer i øjenregionen. Derudover fremhaever resultaterne vigtigheden af undersøgelsen af MYC/BCL2 faenotypen og implementeringen af MYD88 mutationsundersøgelsen i rutinediagnostikken af storcellede B-celle lymfomer i øjenregionen.
    Journal • IO biomarker
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • CD79B (CD79b Molecule)
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    MYD88 mutation • BCL2 expression • MYC expression • CD79B mutation • BCL6 rearrangement • CD79B mutation • BCL2 rearrangement
    2years
    Development of Amino Acid-Modified Biodegradable Lipid Nanoparticles for siRNA Delivery. (PubMed, Acta Biomater)
    Moreover, the LHHK LNP encapsulating IKBKE siRNA inhibits cell proliferation and suppresses tumor growth of pancreatic cancer in vivo. These results suggest that amino acid-modified lipids possess a great potential for siRNA delivery in cancer therapy.
    Journal
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    IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    2years
    CD24 Expression Dampens the Basal Antiviral State in Human Neuroblastoma Cells and Enhances Permissivity to Zika Virus Infection. (PubMed, Viruses)
    Transcriptomics analysis revealed that CD24 expression decreased expression of genes involved in intracellular antiviral pathways, including IFN-I, NFκB, and Ras. Our findings that CD24 expression in neuroblastoma cells represses intracellular antiviral pathways support the proposal that CD24 may represent a novel biomarker in cancer cells for susceptibility to oncolytic viruses.
    Journal • IO biomarker
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    CD24 (CD24 Molecule) • IRF1 (Interferon Regulatory Factor 1) • STAT1 (Signal Transducer And Activator Of Transcription 1)
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    IRF1 expression • CD24 expression
    2years
    Sanguinarine Inhibition of TNF-α-Induced CCL2, IKBKE/NF-κB/ERK1/2 Signaling Pathway, and Cell Migration in Human Triple-Negative Breast Cancer Cells. (PubMed, Int J Mol Sci)
    These effects are related to the compound's ability to inhibit the angiogenic CCL2 and impact the ERK1/2 pathway. Therefore, SANG use may be recommended as a component of the therapeutic strategy for TNBC.
    Journal
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    TNFA (Tumor Necrosis Factor-Alpha) • CCL2 (Chemokine (C-C motif) ligand 2) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    over2years
    Effects of Diallyl Trisulfide on TNF-α-stimulated Genetically different Triple-Negative Breast Cancer Cells. (PubMed, FASEB J)
    The data show that genetically different cells may respond in a different way to DATS treatment. In conclusion, DATS may be a potential candidate for breast cancer therapy to slow TNBC progression.
    Journal
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    IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CCL2 (Chemokine (C-C motif) ligand 2) • CSF2 (Colony stimulating factor 2) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • MAPK8 (Mitogen-activated protein kinase 8)
    |
    IL6 expression
    over2years
    EBV-Induced CXCL8 Upregulation Promotes Vasculogenic Mimicry in Gastric Carcinoma via NF-κB Signaling. (PubMed, Front Cell Infect Microbiol)
    In addition, activation of NF-κB signaling was involved in VM formation induced by CXCL8, which was blocked by NF-κB inhibitors BAY 11-7082 and BMS345541. Finally, CXCL8 is positively correlated with overall survival in GC patients. In conclusion, EBV-upregulated CXCL8 expression promotes VM formation in GC via NF-κB signaling, and CXCL8 might serve as a novel anti-tumor target for EBVaGC.
    Journal
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    CXCL8 (Chemokine (C-X-C motif) ligand 8)
    |
    CXCL8 expression • CXCL8 overexpression
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    BMS-345541 • Bay11-7082
    over2years
    The Multi-Kinase Inhibitor EC-70124 Is a Promising Candidate for the Treatment of FLT3-ITD-Positive Acute Myeloid Leukemia. (PubMed, Cancers (Basel))
    Several tyrosine kinase/FLT3 inhibitors have been developed and tested clinically, but very few (midostaurin and gilteritinib) have thus far been FDA/EMA-approved for patients with newly diagnosed or relapse/refractory FLT3-ITD AML. Orally disposable EC-70124 exerted a potent inhibitory effect on the growth of FLT3-ITD AML cells, delaying disease progression and debulking the leukemia. Collectively, our findings show that EC-70124 is a promising and safe agent for the treatment of AML with FLT3-ITD.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    Xospata (gilteritinib) • Rydapt (midostaurin) • EC-70124
    over2years
    DDX3X functionally and physically interacts with estrogen receptor-alpha. (PubMed, Biochim Biophys Acta Gene Regul Mech)
    Based on our data, we propose that DDX3X acts as an adaptor to facilitate IKKε-mediated ERα activation, akin to the mechanism we previously elucidated for IKKε-mediated Interferon Regulatory factor 3 (IRF3) activation in innate immune signalling. In conclusion, our research provides a novel molecular mechanism that might contribute to the oncogenic effect of DDX3X in breast cancer, potentially linking it to the development of resistance against endocrine therapy.
    Journal
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    ER (Estrogen receptor) • DDX3X (DEAD-Box Helicase 3 X-Linked)
    |
    tamoxifen
    over2years
    The potential value of amlexanox in the treatment of cancer: molecular targets and therapeutic perspectives. (PubMed, Biochem Pharmacol)
    The anticancer potency is generally modest but largely enhanced upon combination with cytotoxic (temozolide, docetaxel), targeted (selumetinib) or biotherapeutic agents (anti-PD-1 and anti-CTLA4 antibodies). Altogether, the analysis provides a survey of the anticancer action of AMX, with the implicated protein targets. The use of this well-tolerated drug to treat cancer should be further considered and the design of newer analogues encouraged.
    Review • Journal
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    IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1) • S100A4 (S100 calcium binding protein A4)
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    docetaxel • Koselugo (selumetinib) • Aphthasol (amlexanox)
    almost3years
    Prognosis-related autophagy genes in female lung adenocarcinoma. (PubMed, Medicine (Baltimore))
    At last, there is autophagy genes differentially expressed among various clinicopathological parameters: ATG4A, BAK1, CCR2, DLC1, ERO1A, FKBP1A, ITGA6.The risk score can be used as an independent prognostic indicator for female patients with lung adenocarcinoma. The autophagy genes ITGA6, ERO1A, FKBP1A, BAK1, CCR2, FADD, EDEM1, ATG10, ATG4A, DLC1, VAMP7, ST13 were identified as prognostic genes in female lung adenocarcinoma, which may be the targets of treatment in the future.
    Journal • PARP Biomarker
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NRG1 (Neuregulin 1) • BIRC5 (Baculoviral IAP repeat containing 5) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • FADD (Fas associated via death domain) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • NRG3 (Neuregulin 3) • PPP1R15A (Protein Phosphatase 1 Regulatory Subunit 15A) • ERO1A (Endoplasmic Reticulum Oxidoreductase 1 Alpha) • GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • BAK1 (BCL2 Antagonist/Killer 1) • ITGA6 (Integrin, alpha 6)
    almost3years
    IKBKE phosphorylates and stabilizes Snail to promote breast cancer invasion and metastasis. (PubMed, Cell Death Differ)
    Mechanistically, IKBKE tightly controls the stability of transcriptional factor Snail in different layers, in particular by directly phosphorylating Snail, which markedly blocks the E3 ligase β-TRCP1-mediated Snail degradation, resulting in breast cancer epithelial-mesenchymal transition (EMT) and metastasis. These findings together reveal a novel oncogenic function of IKBKE in promoting breast cancer metastasis by governing Snail abundance, and highlight the potential of targeting IKBKE for metastatic breast cancer therapies.
    Journal
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    IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    almost3years
    Effect of Diallyl Trisulfide on TNF-α-induced CCL2/MCP-1 Release in Genetically Different Triple-negative Breast Cancer Cells. (PubMed, Anticancer Res)
    DATS may have a role in TNBC therapy and prevention by targeting CCL2.
    Journal
    |
    IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CCL2 (Chemokine (C-C motif) ligand 2) • CSF2 (Colony stimulating factor 2) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • MAPK8 (Mitogen-activated protein kinase 8)
    |
    IL6 expression
    3years
    Silencing IKBKE inhibits the migration and invasion of glioblastoma by promoting Snail1 degradation. (PubMed, Clin Transl Oncol)
    Our studies suggest that the IKBKE-Snail1 axis may serve as a potential therapeutic target for GBM treatment.
    Journal
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    IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    3years
    CYT387, a potent IKBKE inhibitor, suppresses human glioblastoma progression by activating the Hippo pathway. (PubMed, J Transl Med)
    In subsequent in vivo experiments, we found that CYT387 inhibited subcutaneous nude mouse tumor growth but had little impact on intracranial orthotopic xenografts, probably due to a limited ability to penetrate the blood-brain barrier (BBB). These results suggest that CYT387 has potential as a new antiglioblastoma drug, but an approach to allow passage through the blood-brain barrier (BBB) is needed.
    Journal
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    YAP1 (Yes associated protein 1) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
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    Ojjaara (momelotinib)
    3years
    BCMA-specific ADC MEDI2228 and Daratumumab induce synergistic myeloma cytotoxicity via enhanced IFN-driven innate immune responses and expression of CD38 and NKG2D ligands (IMW 2021)
    It overcame CD38 downregulation triggered by IL6 and bone marrow stromal cell culture supernatant (BMSC- sup), via activation of STAT1-IRF1 without phosphorylation of STAT3 in immunomodulatory drugs (IMiDs)- and bortezomib-resistant MM cell lines. Taken together, our data showed that MEDI2228 restored MM sensitivity to CD38 targeting by Dara without depleting NK cells and potentiated immunogenic cell death of MM cells. These results therefore provide the mechanistic rationale for clinical evaluation of combination CD38- and BCMA-directed immunotherapies to further improve patient outcome in MM.
    IO biomarker
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    IL6 (Interleukin 6) • CD38 (CD38 Molecule) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • STING (stimulator of interferon response cGAMP interactor 1) • CCR7 (Chemokine (C-C motif) receptor 7) • CCL2 (Chemokine (C-C motif) ligand 2) • CSF2 (Colony stimulating factor 2) • GZMB (Granzyme B) • SOCS1 (Suppressor Of Cytokine Signaling 1) • IFIT1 (Interferon Induced Protein With Tetratricopeptide Repeats 1) • RUNX3 (RUNX Family Transcription Factor 3) • STAT1 (Signal Transducer And Activator Of Transcription 1) • CCL22 (C-C Motif Chemokine Ligand 22) • CGAS (Cyclic GMP-AMP Synthase) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • NKG2D (killer cell lectin like receptor K1)
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    CD38 expression • IRF1 expression
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    bortezomib • Darzalex (daratumumab) • MEDI2228
    over3years
    Integrative Characterization of Immune-relevant Genes in Hepatocellular Carcinoma. (PubMed, J Clin Transl Hepatol)
    Correlation analysis indicated TNFSF4 , LGALS9 , KIAA1429 , IDO2, and CD276 were closely related to the risk score, and CD4 T cells, macrophages, and neutrophils were the primary immune infiltration cell types. Our results highlight the importance of immune genes in the HCC microenvironment and further unravel the underlying molecular mechanisms in the development of HCC.
    Journal
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    PD-1 (Programmed cell death 1) • CD276 (CD276 Molecule) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • CD4 (CD4 Molecule) • NRF1 (Nuclear Respiratory Factor 1) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    over3years
    Anti-Metastatic and Anti-Angiogenic Effects of Curcumin Analog DK1 on Human Osteosarcoma Cells In Vitro. (PubMed, Pharmaceuticals (Basel))
    Whilst for MG-63, the significantly down-regulated oncogenes were Serpin E1, AKT2, VEGF, uPA, PD-ECGF, and Endoglin. These results suggest that curcumin analog DK1 may serve as a potential new anti-osteosarcoma agent due to its anti-metastatic and anti-angiogenic attributes.
    Preclinical • Journal
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    PTEN (Phosphatase and tensin homolog) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • COL1A1 (Collagen Type I Alpha 1 Chain) • IGFBP2 (Insulin-like growth factor binding protein 2) • ENG (Endoglin) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • NFKBIA (NFKB Inhibitor Alpha 2) • NFKBIE (NFKB Inhibitor Epsilon) • MMP3 (Matrix metallopeptidase 3)
    over3years
    NF-кB pathway genes expression in chicken erythrocytes infected with Avian Influenza virus subtype H9N2. (PubMed, Br Poult Sci)
    However, IFN-α and TRAF6 were down-regulated at 10 h post-infection.4. These results give initial evidence that the NF-κB pathway, and other genes related to immunity, in chicken erythrocytes may contribute to LPAIV subtype H9N2 and induce host immune responses.
    Journal
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    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IFIH1 (Interferon Induced With Helicase C Domain 1) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • NFKBIA (NFKB Inhibitor Alpha 2) • NFKBIE (NFKB Inhibitor Epsilon)
    over3years
    Insulin-like growth factor binding protein 3 promotes radiosensitivity of oral squamous cell carcinoma cells via positive feedback on NF-κB/IL-6/ROS signaling. (PubMed, J Exp Clin Cancer Res)
    Our data demonstrate that IGFBP3, a potential biomarker for radiosensitivity, promotes IR-mediated OSCC cell death by increasing ROS production through NF-κB activation and cytokine production.
    Journal
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    IL6 (Interleukin 6) • IGFBP3 (Insulin-like growth factor binding protein 3)
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    BMS-345541
    over3years
    Amlexanox Enhances Temozolomide-Induced Antitumor Effects in Human Glioblastoma Cells by Inhibiting IKBKE and the Akt-mTOR Signaling Pathway. (PubMed, ACS Omega)
    These results suggest that amlexanox sensitized the primary glioma cells and U87 MG cells to TMZ at least partially through the suppression of IKBKE activation and the attenuation of TMZ-induced Akt activation. Overall, combined treatment with TMZ and amlexanox may provide a promising possibility for improving the prognosis of glioblastoma patients in clinical practice.
    Journal
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    IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
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    AMPK expression
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    temozolomide • Aphthasol (amlexanox)
    almost4years
    Macrophages confer resistance to BET inhibition in triple-negative breast cancer by upregulating IKBKE. (PubMed, Biochem Pharmacol)
    Here, we found that BETi JQ1 and I-BET151 exerted anti-tumor effects in TNBC by decreasing IKBKE expression to attenuate NF-κB signaling. Altogether, our findings illustrated TNBC-activated macrophages conferred TNBC cells resistance to BETi via IL-6 or IL-10/STAT3/IKBKE/NF-κB axis. Blockade of IKBKE or double inhibition of BET and STAT3 might be a novel strategy for treatment of TNBC.
    Journal
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    IL6 (Interleukin 6) • IL10 (Interleukin 10) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
    |
    JQ-1 • I-BET151
    almost4years
    TBK1, a central kinase in innate immune sensing of nucleic acids and beyond. (PubMed, Acta Biochim Biophys Sin (Shanghai))
    An atlas of TBK1 substrates is in constant expanding, setting TBK1 as a key node of signaling network and a dominant player in contexts of cell biology, animal models, and human diseases. Here, we review recent advancements of activation, regulations, and functions of TBK1 under these physiological and pathological contexts.
    Journal
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    STING (stimulator of interferon response cGAMP interactor 1) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)