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Amlexanox inhibits TBK1. 40 / 41
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"We treated WT mice with Amlexanox, which blocks TBK1 activity in vivo without affecting the activity of IKK-α or IKK-β or any other known kinases (52, 53)."
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"Consistent with this view, global knockout of the cGAS-cGAMP-STING downstream target TBK1 or IRF3, or pharmacological inhibition of IkappaB kinase epsilon (IKKepsilon) and TBK1 by amlexanox, reduced body weight, enhanced insulin sensitivity, and improved glucose tolerance in obese mice and in a subset of patients with type 2 diabetes."
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"Thus, chronic decrease in Tbk1 activity is hypothesized to be associated with increased inflammatory responses.The anti-inflammatory agent Amlexanox (AMX; Reilly et al., 2013) is an inhibitor of Tbk1 and of the closely related IKK-ε (Cheng H. et al., 2018)."
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"Consistent with this view , global knockout of the cGAS-cGAMP-STING downstream target TBK1 ( 37 ) or IRF3 ( 38 ) , or pharmacological inhibition of IkappaB kinase epsilon ( IKKepsilon ) and TBK1 by amlexanox , reduced body weight , enhanced insulin sensitivity , and improved glucose tolerance in obese mice and in a subset of patients with type 2 diabetes ( 34,39 ) ."
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"Inhibition of TBK1/IKKε with two different small molecules, amlexanox (Fig. 8A and Fig. S4) or BX-795 (Fig. S4), also reduced poly(I:C)-induced Akt P-S473, demonstrating that TBK1/IKKε activity positively controls mTORC2 signaling to Akt in RAW264.7 macrophages.We next isolated primary bone marrow derived macrophages (BMDMs) from Mtor and Mtor mice."
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"In vitro studies revealed that amlexanox blocks TBK1 as well [XREF_BIBR]."
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"Accordingly, inhibition of TBK1 by amlexanox reduced p62 aggregates and restored NSC maintenance and differentiation in Fip200 hGFAP cKO mice."
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"Amlexanox has been shown to down-regulate the immune system and attenuate downstream TBK1 signaling (50)."
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"Our study shows that inhibition of TBK1 by amlexanox could alleviate PQ-induced ALI, which has potential for future therapeutic strategies.TBK1 plays a vital role in the pathogenesis of PQ-induced ALI[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Recently, Reilly et al. [XREF_BIBR] discovered a small molecule inhibitor of IKKepsilon and TBK1 kinases called amlexanox, which has been shown to selectively inhibit both IKKepsilon and TBK1."
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"Amlexanox and BAY 11-7082 were used to inhibit TBK1 and NF-κB, respectively."
34570917
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"Thus, we also tried to focus on KCs and found that amlexanox treatment reduced the activities of TBK1 and IKKε in PA-stimulated KCs."
32905826
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"However, since amlexanox inhibits both IKKε and TBK1, the impact of TBK1 on melanoma needs to be further investigated.To further elucidate the effects of IKKε inhibition on melanoma growth and cancer-[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Recently, amlexanox has been shown to inhibit TBK1 and IKKepsilon, both of which are induced in the liver and fat by high-fat diet mediated NF-kappaB activation [XREF_BIBR]."
27353409
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"Our study provides evidence that TBK1 inhibition by amlexanox alleviates PQ-induced ALI and may be a new therapeutic strategy ."
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"In line with this, a small molecule inhibitor of TBK1/IKKε axis, amlexanox, showed increased thermogenesis accompanied by elevated energy expenditure."
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"Finally, we tested amlexanox (AMX) which inhibits 204 TANK binding kinase 1 (TBK1) and its adaptor protein TBK-binding protein 1 (TBKBP1) which 205 has been reported to variously regulate Rab7a activity (19) or induction of IFN response genes 206 (20)."
| DOI
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"Inhibition of TBK1 by amlexanox protects against liver fibrosis induced by CCl4 (Zhou et al., 2020)."
35924048
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"USP38-TG mice were intraperitoneally injected with Amlexanox (an inhibitor of TBK1) or DMSO 2 weeks after AB surgery (Figure 10A)."
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"Amlexanox 98 inhibits IKKε and TBK1 to improve insulin sensitivity (IC 5800 and 800 nM)."
38139019
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"In hPRCs, we observed that inhibition of TBK1 by Amlexanox leads to significant inhibition of cell death induced by M98K-OPTN and E50K-OPTN."
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"Inhibition of TBK1 by amlexanox attenuates paraquat-induced acute lung injury."
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"Specifically, amlexanox inhibition of TBK1/IKKε was identified as a novel therapeutic intervention for inflammatory and nephrotoxic tubulointerstitial kidney injury.TI-IFNs are thought to contribute to the pathogenesis of viral or autoimmune glomerulonephritis."
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"Amlexanox, which is known to inhibit TBK1 and IKKepsilon selectively, is an approved drug for the treatment of bronchial asthma, allergic rhinitis, and conjunctivitis in Japan and elsewhere."
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"Cells were pretreated with amlexanox (50 or 100 μM) for 1 h, treated with poly I:C and then stimulated with IFN-γ for 48 h. Amlexanox at 100 μM reduced the augmentation of IFN-γ-induced NO production [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"A study published in 2019 by Quan et al. provides evidence that amlexanox inhibits TBK1, thus inhibiting dendritic cell maturation and decreasing inflammation caused by the innate immune response on a standard mouse model [XREF_BIBR]."
33380937
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"Amlexanox is a specific inhibitor of IKKepsilon and TBK1."
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"Because amlexanox inhibits TBK-1, this evidence potentially points to an indirect pathway in which amlexanox increases the secretion of IL-6 from adipocytes through a cAMP / p38 dependent pathway."
33380937
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"Inhibition of IKKepsilon or TBK1 (data not shown) by amlexanox was competitive for its substrate ATP (XREF_FIG), indicating that it interacts with the enzymes in the ATP binding site."
23396211
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"Blocking TBK1 and IKKepsilon during transduction of NK cells enabled their efficient transduction by VSV-G LVs as judged by YFPexpression of 40-50%, with half maximal effective concentrations of 1.1 microM (MRT67307), 5 microM (BX-795) and 24.8 microM (amlexanox)."
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"Collectively, these studies show that IKBKE plays a pivotal role in human malignancy and could be a critical therapeutic target for PDAC.Recent studies have identified two small-molecule compounds, amlexanox and CYT387, which directly inhibit IKBKE/TBK1 kinase activity [10,18,19]."
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"Möller et al. found that TBK1 and IKKε inhibition by amlexanox was involved in the reduced proliferation, migration, and invasion of melanoma cells, as well as also significantly suppressing autophagy[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In contrast, we herein showed a pivotal and differential role of IKKε and TBK1 in promoting APAP-induced ALI progression: In the present study, we demonstrated that amlexanox inhibition of IKKε and TB[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Amlexanox blocks activity of TBK1 and IKKepsilon with a half maximal inhibitory concentration (IC50) of approximately 1-2 muM."
30791439
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"Amlexanox, an inhibitor of RLR signaling pathway, specifically supresses the noncanonical IkB kinases IKKε and TBK1, and both are essential players for the coordination of IFN regulatory factor 3 (IRF3)- and NF-κB-mediated innate immune response [27, 28]."
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"Apilimod (10 and 100 nM) or Amlexanox (1 and 5 μM) was added to inhibit PIKfyve and TBK1 respectively."
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"Amlexanox can inhibit effectively the activity of TBK1 and IKKε, increase the sensitivity of catecholamines in adipose tissue to achieve weight loss, and reduce inflammation of adipose tissue caused b[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34051368
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"Inhibition of TBK1 by amlexanox attenuates paraquat-induced acute lung injury ."
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"61 He et al. demonstrated that, in hepatic stellate cells (HSCs) of NAFLD induced by HFD + LPS, TBK1 inhibition by amlexanox can attenuate hepatic steatosis and maintain the homeostasis of glucose and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"However, activated TBK1 in the form of phosphorylation, was inhibited by amlexanox in mouse lungs and RAW264.7 cells."
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