Mechanistically, TBK1 deletion or inhibition by amlexanox or GSK8612 reduced the expression of the transcription factor interferon-regulatory factor (IRF)4 and increased the level of IRF5 activation in macrophages stimulated with M-CSF, leading to an M1-like profile with highly proinflammatory factors. IRF5 deletion reversed the effect of TBK1 inhibition on M-CSF-mediated macrophage polarization. Our findings suggest that TBK1 contributes to the regulation of macrophage polarization in response to M-CSF stimulation partly through the IRF5/IRF4 axis.

In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD.

These findings suggest CU06-1004 as a potential therapeutic agent for folic acid-induced AKI.

P2, N=7, Terminated, University of Michigan | N=15 --> 7 | Suspended --> Terminated; Due to limited funding, trial was suspended, intending to restart with additional funds; then preliminary results were obtained, and research moved on to placebo controlled trial. Results for both have been published.

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.

Notably, the HDIL-2 and CU06-1004 combination therapy considerably reduced tumor growth in the B16F10 melanoma mouse model. Our data suggest that CU06-1004 acts as a potential anticancer drug candidate, not only by preventing HDIL-2-induced VLS but also by enhancing the anticancer effects of HDIL-2 immunotherapy.

Melphalan 200 mg/m2 was given on day -1. Antibacterial prophylaxis (oral vancomycin and ciprofloxacin) was administered from the onset of neutropenia (days 5-8 in this trial) until neutrophil recovery to 0.5 k/uL or fever. Cefepime and metronidazole were used for neutropenic fever...ALDEx2 was used for differential abundance analysis... HBOT may affect salivary and fecal microbiota composition. HBOT appeared to decrease microbiota diversity loss after autologous HCT. Increased oxygen pressure near the intestinal epithelium after HBOT may make the lumen a more favorable habitat for obligate anaerobic commensals, hence their enhanced fecal detection.

Our findings demonstrate that pharmaceutical inhibition of Th2 cell function improves ICB response via remodeling immune landscape of TME, which illustrates a promising combinatorial immunotherapy.

Our mouse model also showed that Amlexanox combined with Olaparib inhibited tumor growth of CRPC xenografts. Our study highlights a new role for IKKε in DNA damage repair through the regulation of Rad51 transcription and provides a rationale for the combination of Amlexanox and Olaparib in the treatment of patients with CRPC.

However, to this point, only momelotinib (MMB)/CYT387 has been evaluated as a cancer therapy in clinical trials, while amlexanox (AMX) has been evaluated clinically for treatment of type II diabetes, nonalcoholic fatty liver disease, and obesity. We also discuss the potential molecular mechanisms of targeting TBK1 for cancer treatment. We hope that our effort can help to stimulate the development of novel strategies for targeting TBK1 signaling in future approaches to cancer therapy.

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.

Our study suggests that targeting IKKε with BX795 or Amlexanox in androgen-independent-PC cells induces a senescence phenotype and demonstrates in vivo anti-tumor activity. These results strengthen the potential of exploiting IKKε as a therapeutic target.

In conclusion, our study showed that Amlexanox or GSK8612 was effective in inhibiting TBK1 expression leading to decreased cell proliferation and colony formation in GBM cell lines. A synergistic effect was observed with each of these TBK1 inhibitors plus radiation and/or TMZ. These results suggest that TBK1 may be a potential candidate to pursue as novel therapeutic target in IDH wild-type gliomas. Future work will focus on in vivo studies with Amlexanox or GSK8612 alone and in combination with TMZ and radiation AUTHOR DISCLOSURE: Z. Tong: None.

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.

Our study indicated that the immune-related prognostic signature could serve as a novel biomarker for predicting patients' prognosis and providing new immunotherapy targets in ESCA.

In an in vivo xenograft model in nude mice, amlexanox treatment significantly reduced tumor growth. In conclusion, amlexanox was able to suppress tumor progression potentially by the inhibition of autophagy as well as NF-кB and MAP kinase pathways and might therefore constitute a promising candidate for melanoma therapy.