Small Molecule NF-κB Pathway Inhibitors in Clinic

Ramadass, Venkataramanan; Vaiyapuri, Thamilselvan; Tergaonkar, Vinay

doi:10.3390/ijms21145164

Cited by 149 publications

(103 citation statements)

References 154 publications

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“…NF-κB pathway is a center of inflammation which is widely associated in the regulations and controls of diseases 36, 49 . However, the side effect of NF-κB inhibitors is so strong that they cannot be used in clinical 50 . Here, besides NF-κB inhibitors, we selected several novel inhibitors that may take effects on the MM mouse models.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers and candidate inhibitors for multiple myeloma

Wang

Yuan

2021

Preprint

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Multiple myeloma (MM) is a plasma cell malignancy that causes the overabundance of monoclonal paraprotein (M protein) and organ damages. In our study, we aim to identify biological markers and processes of MM using a bioinformatics method to elucidate their potential pathogenesis. The gene expression profiles of the GSE153626 datasets were originally produced by using the high-throughput Illumina HiSeq 4000 (Mus musculus). The functional categories and biochemical pathways were identified and analyzed by the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), Gene Ontology (GO), and Reactom enrichment. KEGG and GO results showed the biological pathways related to immune dysfunction and signal transduction are mostly affected in the development of MM. Moreover, we identified several genes including Gngt2, Foxp3, and Cd3g were involved in the regulation of immune cells. We further predicted new inhibitors that have the ability to block the progression of MM based on the L1000fwd analysis. Therefore, this study provides further insights into the underlying pathogenesis of MM.

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Section: Discussionmentioning

confidence: 99%

Identification of biomarkers and candidate inhibitors for multiple myeloma

Wang

Yuan

2021

Preprint

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“…Therefore, Calu-3 and H322M cells were selected for the following experiments. Inhibition of NF-B signaling has a potential therapeutic role in alleviating the severe form of COVID-19 through reduction in the cytokine storm (15). To further explore whether NF-B pathway also play a role in ACE2 regulation, PDTC, an inhibitor of NF-B activation, was used to treat cells and the cytotoxic effect of PDTC was investigated by MTS assay.…”

Section: Nf-b Inhibitor Pdtc Decreases Endogenous Ace2 Expressionsmentioning

confidence: 99%

Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro

Lee

Chen

Hsu

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a vast number of infections and fatalities worldwide. As the development and safety validation of effective vaccines are ongoing, drug repurposing is most efficient approach to search FDA approved agents against coronavirus disease 2019 (COVID-19). In the present study, we found that endogenous ACE2 expressions could be detected in H322M and Calu-3 cell lines, as well as their ACE2 mRNA and protein expressions were suppressed by pyrrolidine dithiocarbamate (PDTC), a NF-kappa B inhibitor, in dose- and time-dependent manners. Moreover, N-acetyl-cysteine (NAC) pretreatment reversed PDTC-induced ACE2 suppression, as well as the combined treatment of hydrogen peroxide and knockdown of p50 subunit of NF-kappa B by siRNA reduced ACE2 expression in H322M cells. In addition, anthelmintic drug triclabendazole and antiprotozoal drug emetine, repurposed drugs of NF-kappa B inhibitor, also inhibited ACE2 mRNA and protein expressions in H322M cells. Moreover, zinc supplement augmented the suppressive effects of triclabendazole and emetine on ACE2 suppression in H322M and Calu-3 cells. Taken together, these results indicate that ACE2 expression is modulated by reactive oxygen species (ROS) and NF-kappa B signal in human lung cell lines, and zinc combination with triclabendazole or emetine has the clinical potential for the prevention and treatment of COVID-19.

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“…Furthermore, IKKα deletion can lead to increased resistance to HCV infection and ability for hepatocyte proliferation and liver regeneration. 50 , 59 Teglarinad chloride, one of the IKKα/ IKKβ inhibitors which has passed phase 1 clinical trials for malignant melanoma, lymphoma and solid tumors, 67 may be used in treatment of HCV infection and acute liver failure. Although some specific inhibitors and/or monoclonal antibodies are currently being applied to a broad range of diseases in which aberrant activation of noncanonical NF-κB signaling occurs, further studies are needed to determine whether they can be used in the treatment of liver diseases.…”

Section: Therapeutic Targeting Of the Noncanonical Nf-κb Signaling Pamentioning

confidence: 99%

Noncanonical NF-κB Signaling Pathway in Liver Diseases

Chen

Zhang

2020

Journal of Clinical and Translational Hepatology

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The noncanonical NF-κB signaling pathway is an important branch of NF-κB signaling. It is involved in regulating multiple important biological processes, including inflammation and host immune response. A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase (NIK), which activates the downstream kinase IKKα to process p100 to p52, thereby forming the RelB/p52 heterodimer to initiate the expression of target genes. Currently, many specific inhibitors and monoclonal antibodies targeting or triggering this pathway are being developed and tested for various diseases, including cancers, autoimmune diseases, and virus infection. Given that aberrant activation of the noncanonical NF-κB pathway is frequently observed in various liver diseases, targeting this pathway may be a promising therapeutic strategy to alleviate liver inflammation. Moreover, activation of this pathway may contribute to the antiviral immune response and promote the clearance of persistent hepatotropic virus infection. Here, we review the role of the noncanonical NF-κB pathway in the occurrence and development of different liver diseases, and discuss the potency and application of modulating the noncanonical NF-κB pathway for treatment of these liver diseases.

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Small Molecule NF-κB Pathway Inhibitors in Clinic

Cited by 149 publications

References 154 publications

Identification of biomarkers and candidate inhibitors for multiple myeloma

Identification of biomarkers and candidate inhibitors for multiple myeloma

Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro

Noncanonical NF-κB Signaling Pathway in Liver Diseases

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