etomoxir (MIQ-001)

The addition of the inhibitor of FAO (Etomoxir) reversed the above trends...In summary, our results suggested that KLF5 affects anoikis in GC cells by targeting NTSR1 to modulate the FAO pathway. Therefore, blocking the FAO pathway regulated by the KLF5/NTSR1 axis may become a new strategy for the treatment of GC.

Fatty acid oxidation (FAO) dependency was assessed by lipid imaging, mitochondrial activity analysis, and pharmacological inhibition with etomoxir...CD36+ CTCs drive immune evasion and metastasis in PD-1-resistant NSCLC through FAO-dependent metabolic reprogramming. Targeting this metabolic vulnerability may enhance the efficacy of immunotherapy.

Conversely, inhibition of CPT1 by etomoxir caused increased intracellular Dox retention, leading to Dox-induced cytotoxicity and attenuating the invasiveness of TNBC cells. Taken together, Dox-resistance reprograms cellular metabolism towards FAO regulatory circuit sustaining the mitochondrial bioenergetics, promoting drug efflux, and accentuating breast cancer progression. Based on these findings, it is possible that FAO inhibitors effectively combat drug-induced TNBC chemoresistance.

Also, etomoxir, a carnitine palmitoyl transferase (CPT)1 inhibitor, decreased PA- and MTDH-Wt/Δ7-induced TNBC cell invasive potential...Further, SCID mice bearing sh.MTDH-Wt or sh.MTDHΔ7-MDA-MB-231cells fed a high-fat diet (HFD) showed significant resistance to tumor growth and metastatic spread compared to mice bearing parental MDA-MB-231 cells fed either HFD or chow diet. In conclusion, this study highlights a novel mechanism by which PA or HFD can promote TNBC aggressiveness through MTDH-mediated upregulation of mitochondrial FAO.

Treatment with the CPT1A inhibitor Etomoxir further confirmed this mechanism by blocking lipid transfer into the mitochondria and suppressing fatty acid oxidation, resulting in lipid accumulation. In addition, it was found that inhibition of BRD9 reduced ICC tumor growth and could help overcome chemoresistance. Together, the results suggest the potential of BRD9 as a therapeutic target for intrahepatic cholangiocarcinoma and highlights its role in regulating fatty acid metabolism in cancer cells.

This effect was abrogated by etomoxir, an irreversible inhibitor of CPT1, the rate-limiting enzyme of the carnitine shuttle, highlighting a CPT1-dependent mechanism for lipid mobilization. Together, these findings reveal a previously unrecognized role for mitochondrial lipid metabolism in ALS pathogenesis and identify a therapeutic pathway for mitigating the cytotoxic consequences of lipid and acylcarnitine accumulation in FUS-associated ALS.

Perioperative inhibition of NET formation utilizing DNAse, GSK484, or PAD4 knockout mice prevented surgically induced tumor growth, whereas pre-treating cancer cells with NETs in vitro before inoculation increased tumor burden...Blocking FAO with etomoxir, a CPT1α inhibitor, prevented metastatic tumor growth induced by surgical NETs...Analysis of patient data substantiated the correlation between NET abundance and lipid metabolism, and plasma from post-operative patients upregulated CD36 expression and promoted the proliferation of colorectal cancer cells. Together, these findings show that the systemic NETosis response triggered by surgery promotes tumor progression by activating the MYC transcriptional program and reprogramming FAO metabolism in cancer cells.

Inhibition of CPT1A, either by siRNA-mediated knockdown or by etomoxir, reduces the migratory and invasive properties of the OC cells...Finally, inhibiting CPT1A successfully attenuates TGFβ-induced EMT in ovarian cancer cells. Cumulatively, our study underscores the role of CPT1A-mediated FAO in facilitating ovarian cancer progression through TGFβ-induced EMT.

Mild mitochondrial inhibition induced by low-dose etomoxir or signals from tumor-associated macrophages altered the lipidome and triggered the downstream transcriptional program of PPAR-δ...Notably, genetic or pharmacological inhibition of PPAR-δ prevented this metabolic rewiring and suppressed both invasiveness in vitro and metastasis in vivo. These findings establish PPAR-δ as a central driver of metabolic reprogramming in response to starvation and tumor microenvironmental cues that promotes a pro-metastatic phenotype in PDAC, suggesting that PPAR-δ inhibition could serve as a therapeutic strategy to combat PDAC progression.

Treatment with the CPT1A inhibitor etomoxir (50 μM) reversed the increased FAO induced by STING depletion in KYSE-30 cells...In addition, STING knockout in 4-NQO-induced ESCC mice led to accelerated tumor progression, which could be mitigated by CPT1A inhibition. Our results suggest that reduced STING expression enhances FAO and promotes ESCC cell proliferation, implicating FAO suppression as a potential therapeutic strategy for ESCC.

This study provides the first evidence of cisplatin concentration-dependent metabolic reprogramming during NSCLC-to-SCLC transformation. We identified a phenotypic transition from NSCLC to SCLC accompanied by a metabolic shift from glucose to fatty acid metabolism, offering new insights into therapeutic strategies for treatmentresistant lung cancer.

We suggest that the MDS BM microenvironment disrupts MSCs metabolism by increasing the expression of CPT-1A, which impairs the ability to support normal HSCs. Interestingly, the suppressive effect is mediated by exosomes rich in CPT-1A, which derived from MSCs. These findings provide novel insights into MDS MSCs-metabolism-Exosome axis in ineffective hematopoiesis and offer new strategies for the treatment of MDS.