etomoxir (MIQ-001) / Meta-IQ, Numiera Therapeutics - LARVOL DELTA

ACADS-dependent fatty acid oxidation drive mitochondrial remodeling in pancreatic cancer cells (AACR 2026) - "Carnitine Palmitoyltransferase 1 (CPT1) was inhibited using Etomoxir (5-100 μM, 24 hrs)...CPT1 blockade also triggered metabolic stress, evidenced by increased phosphorylated AMP-activated protein kinase alpha (p-AMPKα), and resulted in a dose-dependent increase in Dynamin-Related Protein 1 (DRP1), indicating enhanced mitochondrial fission and dysfunction. Collectively, our preliminary data suggests that PDAC cells depend on intact fatty-acid oxidation to maintain mitochondrial integrity."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Targeting CPT‑1‑mediated fatty acid oxidation causes radiation sensitization in glioblastoma (AACR 2026) - "These results suggest that inhibition of CPT‑1‑mediated FAO with perhexiline or etomoxir enhances radiation induced cell death, suppresses sphere forming capacity, and downregulates key GSC markers in both standard and patient-derived GBM models. These findings should be investigated further and suggest that CPT‑1 blockade could be integrated with current standard of care regimens to overcome stem cell driven radiation resistance."

Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CD44 • NES • VIM

Metabolic crosstalk between fatty acid oxidation and glycolysis underlies glioblastoma viability (AACR 2026) - "Here, we evaluated the functional relevance of FAO in U251 GB cells using etomoxir (ETO), a CPT1A inhibitor...These findings indicate that FAO serves as a relevant energy source in GB cells and that its inhibition triggers increased glycolytic flux as a compensatory mechanism. Together, our data reveal a targetable FAO-glycolysis crosstalk in GB and support the therapeutic potential of dual metabolic pathway inhibition to exploit GB metabolic flexibility."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CPT1A

Fatty acid metabolism supports survival in normoxia and migration upon reoxygenation in lung-metastasizing breast cancer cells (AACR 2026) - "Inhibition of key enzymes in fatty acid metabolism, including de novo fatty acid synthesis (FASN via TVB-3166), esterification (DGAT2 via PF-06424439), lipolysis (ATGL via ATGListatin), and β-oxidation (CPT1A via etomoxir), induced a significantly greater reduction in cell viability of MLg than MLr cells, indicating that dynamic fatty acid synthesis, storage, lipolysis and oxidation are necessary to support survival in MLg cells...Overall, these results support that dynamic and rapid fatty acid turnover in lung-metastatic breast cancer cells is necessary to support survival, with lipids accumulated during hypoxia subsequently mobilized and oxidized to fuel migration upon reoxygenation. These findings identify lipid metabolism as a critical driver of lung-specific metastasis and a promising therapeutic target to reduce metastatic spread and improve outcomes for patients with breast cancer."

Metastases • Breast Cancer • Oncology • Solid Tumor • CPT1A • FASN

A bioluminescent assay for detection of fatty acid oxidation (AACR 2026) - "The assay is sensitive to inhibition by etomoxir, confirming dependence on carnitine palmitoyltransferase (CPT1) activity, a key regulatory step in mitochondrial FAO. After media removal, all steps are performed in an add-and-read format suitable for 96- or 384-well plates, enabling convenient, high-throughput quantification of FAO. AI was used to help construct this abstract."

Oncology

VHL loss-driven accumulation of GCN5L1 drives clear cell Renal Cell Carcinoma by regulating acetylation of mitochondrial proteins and metabolic reprogramming (AACR 2026) - "Interestingly, using etomoxir, an irreversible CPT1a/ β-oxidation inhibitor, we show that the growth repression following GCN5L1 loss is dependent on increased CPT1A expression and activity, directly linking GCN5L1 activity to lipid metabolism and ccRCC growth...Our results identify a novel oncogenic pathway in which unregulated GCN5L1 expression drives mitochondrial lysine hyperacetylation and limits activity of β oxidation pathway enzymes, leading to increased lipid accumulation in ccRCC. Therefore, GCN5L1 could be investigated further as a possible therapeutic target in ccRCC."

Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CPT1A • HIF1A • VHL

A novel role for decadienyl-L-carnitine in pulmonary vascular remodeling and the underlying interventional mechanism of osthole. (PubMed, Chin Med) - "Our study identifies a novel function of C10:2 in promoting pyroptosis and accelerating pulmonary vascular remodeling through activation of the HSP47/NLRP3 axis. Furthermore, we demonstrate that osthole effectively inhibits C10:2/HSP47/NLRP3 axis-induced pyroptosis, thereby alleviating pulmonary vascular remodeling. These findings suggest that C10:2 may serve as a potential biomarker for PH diagnosis and provide a foundation for the development of novel anti-PH therapeutic strategies."

IO biomarker • Journal • Cardiovascular • Hypertension • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • BAX • BCL2 • CASP1 • CASP3 • CCNA2 • CDK2 • GSDMD • IL18 • IL1B • MMP2 • MMP9 • NLRP3 • PCNA • SERPINH1 • TGFB1

High fat diet promotes asthma by inhibiting the differentiation of regulatory T cells via E3 ubiquitin ligase ITCH. (PubMed, Mol Immunol) - "Additionally, treatment with Etomoxir, a CPT-1a inhibitor, diminished Treg proportions and Foxp3 expression. We also revealed that the E3 ubiquitin ligase ITCH, which regulates Treg function, was downregulated at the protein level under HFD conditions, despite unchanged mRNA levels. Overall, our research findings highlight the impact of high-fat diets on Treg function and immune regulation, providing insights for potential therapeutic strategies targeting lipid metabolism in inflammatory diseases like asthma."

Journal • Asthma • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Obesity • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • ACACA • FOXP3

KLF5 modulates NTSR1 to facilitate fatty acid oxidation and repress anoikis in gastric cancer. (PubMed, Genes Genet Syst) - "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."

Journal • Gastric Cancer • Oncology • Solid Tumor • CASP3 • KLF5

CD36-Mediated Fatty Acid Oxidation in CTCs Drives Immune Evasion and Metastasis in NSCLC. (PubMed, Immunol Invest) - "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."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD36 • CTCs • PD-1 • SCARB1

Metabolic Flexibility and Energy Substrate Utilization Regulate Contractility in the Human Myometrium. (PubMed, bioRxiv) - "In oxytocin treated myometrial cells, this decrease was also observed upon BPTES treatment in addition to UK5099, suggesting that contractile myometrial cells can shift energy production from glucose to glutamine. Functionally, myometrial contractility was significantly reduced by UK5099 but not by etomoxir, further indicating dependence on glucose utilization."

Journal • Hematological Disorders • Postpartum Hemorrhage

Unrestrained fatty acid oxidation triggers heart failure in mice via cardiolipin loss and mitochondrial dysfunction. (PubMed, bioRxiv) - "Pharmacologic inhibition of FAO with etomoxir or oxfenicine restored cardiolipin levels, normalized ETC activity, and prevented cardiac dysfunction in ACC dHKO mice. These findings demonstrate that unrestrained FAO disrupts both lipid and energy homeostasis, culminating in heart failure in this model. Collectively, these results indicate that although FAO is essential for cardiac energy production, therapeutic strategies aimed at stimulating cardiac FAO may be detrimental rather than beneficial in heart failure."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • ACACA • ACACB

Postnatal Osteoblast-Specific Sirt1 Ablation Directs Bone Remodeling and Systemic Glucolipid Homeostasis. (PubMed, J Endocrinol) - "In this study, tamoxifen (TAM)-induced osteoblast-specific Sirt1 conditional knockout (cKO) mice were generated by crossing Col1a1-CreERT2 mice with Sirt1 floxed mice, and these mice exhibited a lower-bone-mass phenotype associated with declined bone formation and accelerated bone resorption. Furthermore, treatment with the β-catenin agonist rescued the impairment of osteoblastic differentiation and FAO caused by Sirt1 knockout, which can be effectively blunted by etomoxir, a clinically approved FAO inhibitor. In conclusion, these data indicate that manipulation of osteoblast Sirt1 involves in fatty acid utilization and systemic glucolipid metabolism through β-catenin signaling."

Journal • Metabolic Disorders • COL1A1 • SIRT1

Protective role of fatty acid oxidation against epithelial barrier dysfunction in allergic asthma. (PubMed, Redox Rep) - "Using a house dust mite (HDM)-induced murine asthma model and HDM, IL-4, IL-13, or TNF-α stimulated human primary bronchial epithelial cells (BECs) and bronchial epithelial (Beas-2b) cells, we modulated FAO with L-carnitine (agonist) and Etomoxir (inhibitor)...In contrast, treatment with L-carnitine significantly alleviated these pathophysiological features in both in vivo and in vitro models. FAO plays a protective role in the occurrence and development of asthma by maintaining airway epithelial cell homeostasis and barrier function."

Journal • Asthma • Immunology • Inflammation • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • CPT1A • IL13 • IL4 • TNFA

PGC-1α Transcriptionally Regulated by ChREBP Mitigates Neuropathic Pain Through Promoting Microglial Fatty Acid Oxidation and Anti-Inflammatory Response. (PubMed, CNS Neurosci Ther) - "ChREBP alleviates NP by enhancing microglial fatty acid oxidation and anti-inflammatory phenotype via PGC-1α transcriptional activation, revealing a novel metabolic-immune axis for potential NP therapy."

Journal • Inflammation • Neuralgia • Pain

Riboflavin Increases Goat Sperm Motility via Enhancement of Mitochondrial β-Oxidation. (PubMed, Biology (Basel)) - "Notably, these enhancements were suppressed by 100 μM etomoxir, a mitochondrial β-oxidation inhibitor, which reduced total motility, ATP Levels, and CPT1 activity after riboflavin supplementation (p < 0.05). These findings indicate that goat sperm at least partly rely on mitochondrial β-oxidation for ATP generation and that riboflavin supplementation enhances mitochondrial metabolism, thereby improving sperm quality."

Journal • ACADVL

Placental-Derived Mesenchymal Stem Cells Triggers Lipid Metabolism in a Rat Model Thioacetamide-Induced Ovarian Disease via Increased CPT1A Expression for Mitochondrial Dynamics. (PubMed, Cells) - "Furthermore, cocultivation of PD-MSCs with etomoxir (CPT1A inhibitor)-treated primary theca cells increased the expression of steroidogenesis...The upregulation of CPT1A and related mitochondrial proteins contributes to enhanced steroidogenesis and restoration of ovarian homeostasis. These findings offer new insights into the application of stem cell therapies for reproductive medicine."

Journal • Preclinical • Inflammation • Metabolic Disorders • Transplantation • CPT1A • HSD3B1 • IL6 • TNFA

Doxorubicin Resistance Reprograms Triple-Negative Breast Cancer Cell Metabolism via the Fatty Acid β-Oxidation (FAO)-CD36 Regulatory Circuit: Relevance of Enhanced FAO on Tumor Cell Invasiveness. (PubMed, Mol Carcinog) - "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."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD36 • PPARA • SCARB1

Palmitic acid fuels triple-negative breast cancer through metadherin-dependent fatty acid β-oxidation: Relevance to high fat diet-induced breast cancer progression. (PubMed, Cell Signal) - "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."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD36 • MTDH • SCARB1 • SIRT3

SNAI2 orchestrates a hypo-oxidative mitochondrial phenotype with elevated FAO dependence in acute myeloid leukemia (ASH 2025) - "These findings were validated using qRT-PCR andimmunoblotting.Seahorse substrate oxidation stress test showed a marked reduction in mitochondrial respiration uponFAO inhibition by etomoxir in SNAI2-OE cells, indicating that SNAI2 drives a heightened reliance on fattyacids as respiratory substrates...Clinically, SNAI2 may serve as a biomarker foridentifying AML patients who are likely to benefit from metabolism-targeted therapies. In summary,SNAI2 promotes leukemic progression through metabolic rewiring, thereby exposing novel therapeuticvulnerabilities exploitable for precision medicine in AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • ACSM3 • MID1 • SDHB • SNAI2

Lipid uptake via FATP2 enhances CAR-t therapy resistance in B-cell acute lymphoblastic leukemia (ASH 2025) - "To assess whether lipidmobilization and mitochondrial import contribute to CAR resistance, we treated isogenic B-ALL cells withthe lipase inhibitor Lalistat-1 (LAL1i) or the CPT1 inhibitor Etomoxir—blocking fatty acid liberation fromlipid droplets or mitochondrial transport of FAO substrates, respectively—during Mock or CAR-T co-culture...Overall, our findings highlight a previously unappreciated link betweenlipid metabolism and CAR-T resistance in B-ALL. Future studies aim to understand the role of LCFAuptake in conventional chemotherapy responses, as well as determine whether pharmacologicalmodulation of lipid uptake could enhance CAR-T efficacy, particularly in TP53-mutant disease."

IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • CD19 • GZMA • SLC27A2

The Characterization of Metabolic Profile and Substrates Dependencies of Richter's Syndrome Cells Open for Translational Opportunities (ASH 2023) - "BPTES, a glutaminase inhibitor, and UK5099, a mitochondrial pyruvate carrier blocker, led to a significant decrease in the oxygen consumption rate and ATP production, while limited effects were observed when treating RS cells with Etomoxir, a fatty acid oxidation inhibitor...Finally, we showed that selective inhibitors of PI3K (duvelisib) and NF-kB (p65 inhibitor), two major regulators of energy metabolism and biosynthetic pathways, by interfering with the activity of these molecules, impacted on RS cells metabolism with a marked reduction of the oxidative phosphorylation and glycolytic cascade. Overall, these data depict the metabolic features of RS cells and their dependency from glucose and glutamine, at variance with CLL cells that mostly depend on fatty acid oxidation, thus suggesting a metabolic rewiring because of disease evolution. Moreover, they provide a proof-of-principle that metabolism can be envisaged as a candidate target for RS using either direct..."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Richter's Syndrome

ZBTB7A Loss Promotes Synthesis of Lipids and Ketone Bodies in Myeloid Leukemia (ASH 2023) - "Moreover, in this context, the ZBTB7A KO cells responded negatively to the inhibition of the CPT1A enzyme by Etomoxir, suggesting that these cells are not dependent on fatty acid oxidation...In summary, we have advanced the understanding of ZBTB7A loss in leukemia metabolism, showing increased lipid and ketone bodies synthesis at the metabolite level. Lipid synthesis enzymes, such as FASN, FADS1, and FADS2 are attractive drug targets for therapeutic applications, especially in combination with standard therapies and glycolysis inhibitors."

Hematological Malignancies • Leukemia • Oncology • ACAT1 • CPT1A • FADS2 • FASN • HMGCS1 • RUNX1 • RUNX1T1 • ZBTB7A

Investigating the Role of PPAR Delta in Alloreactive T Cells (ASH 2024) - "Culturing agonist-treated cells with 3H-palmitate demonstrated an increase in 3H2O production that was inhibitable by etomoxir, confirming a GW501516-driven increase in FAO in allogenically-stimulated cells. Thus, alloreactive CD8 donor T cells appear to adapt to loss of PPARδ through the upregulation of glutamine metabolism and an increased reliance on metabolid fuels provide through the panthothenate pathway. Future work will interrogate the vitamin B5/CoA axis in PPARδ KO alloreactive CD8 T and examine potential upstream influence by AMPK and mTOR, the two primary energy regulators of T cells, with the long-term goal of pinpointing therapeutic targets in reducing GVHD."

Bone Marrow Transplantation • Graft versus Host Disease • Immunology • AMPK • CD4 • CD8 • CPT1A • PLIN2

Integrating Metabolomics and Molecular Pathways to Uncover Therapeutic Vulnerabilities in Richter's Transformation (ASH 2024) - "Moreover, MGA KO cells showed decreased maximal respiration when treated with etomoxir, a fatty-acid oxidation inhibitor, indicating their reliance on lipid substrates...Our studies reveal Gro3P as a metabolite driver of OXPHOS in MGA KO RT via the Mga-Myc-Nme1-Pgp axis. Combining glycerolipid metabolism and OXPHOS targeting may offer effective strategies to conquer RT."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • Richter's Syndrome • MYC • PGP • SF3B1