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

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

Fatty acid oxidation driven by AMPKα-PPARα-CPT1α axis facilitates M2 polarization of tumor-associated macrophages and radiotherapy resistance (SITC 2025) - "Functional studies used pharmacologic inhibition (GW6471 for PPARα, etomoxir for fatty acid oxidation) and genetic knockout models, including macrophage-specific knockout of AMPKα and PPARα-deficient mice...This metabolic reprogramming contributes to immunosuppression and RT resistance. Targeting this pathway reverses TAMs polarization and improves RT efficacy, providing a rationale for combining metabolic inhibitors with RT to overcome tumor immune suppression."

Colorectal Cancer • Oncology • Solid Tumor • CD36 • CD8 • PPARA • SCARB1

Glucose restriction regulates osteoblasts function by modulating mitochondrial activity and lipolysis. (PubMed, J Nutr Biochem) - "Etomoxir (Eto) addition to LG negatively affected mitochondrial function and osteogenesis, suggesting lipid utilization by OBs in LG condition...Finally, inhibition of lipolysis through ATGListatin reduced osteogenesis in LG-treated compared to PG-treated OBs cell cultures. Altogether, these results show that OBs function is modulated by fuel availability and reinforces the fundamental role for lipid utilization in orchestrating OBs metabolism, during energy demand when tissue glucose availability is limited, such as in pathophysiological conditions, including diabetes."

Journal • Diabetes • Metabolic Disorders • MFN2

DELETION OF LYPLAL1 REDUCES CELLULAR UPTAKE OF FATTY ACIDS AND PROMOTES MITOCHONDRIAL Β-OXIDATION TO PROTECT AGAINST METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) (AASLD 2025) - "These cells showed increased levels of FA oxidation in Seahorse analysis and treatment with mitochondrial β-oxidation inhibitor etomoxir restored lipid accumulation in the KO cells... LYPLAL1 LOF variants had a protective effect against human MASLD and decreased intracellular lipid content in a human liver cell line. Increased levels of FA oxidation and decreased FA uptake likely protect against steatosis in LYPLAL1 KO cells."

Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • CD36 • FABP1 • PPARA • SCARB1

STAT3 induced BRD9 activation promotes intrahepatic cholangiocarcinoma progression by enhancing CD36 controlled fatty acid metabolism. (PubMed, Cancer Lett) - "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."

Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CD36 • CPT1A • SCARB1 • STAT3

Targeting lipid droplets in FUS-linked amyotrophic lateral sclerosis mitigates neuronal and astrocytic lipotoxicity. (PubMed, Brain) - "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."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Metabolic Disorders • Oncology • Sarcoma • Solid Tumor • FUS

Surgery-Induced Neutrophil Extracellular Traps Promote Tumor Metastasis by Reprogramming Cancer Cell Lipid Metabolism. (PubMed, Cancer Res) - "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."

Journal • Colorectal Cancer • Metabolic Disorders • Oncology • Solid Tumor • CD36 • SCARB1

ZFHX3 Knockdown Enhances Metabolic Distress in Atrial Myocytes Through Mitochondrial and Calcium Dysregulation: Mitigation by Trimetazidine. (PubMed, Int J Mol Sci) - "ZFHX3 KD cells exhibited a higher acute response in oxygen consumption after Etomoxir injection, upregulated CD36 and phosphorylated ACC expression, increased glucose uptake and lactate production, reduced PDH activity, and higher levels of PDK4 and LDHA. These findings suggest that ZFHX3 downregulation shifts substrate preference toward fatty acid utilization at the expense of glucose oxidation, contributing to metabolic and mitochondrial calcium dysregulation. TMZ mitigates these effects, highlighting its therapeutic potential in AF associated with ZFHX3 deficiency."

Journal • Atrial Fibrillation • Cardiovascular • Metabolic Disorders • CD36 • LDHA • PDK4 • SCARB1 • ZFHX3

Metabolic Hijacking: An MOF-Based Nanoprogrammer Overcomes Drug Resistance in Glioblastoma. (PubMed, Nano Lett) - "Resistance to Temozolomide (TMZ), the most common oral anticancer drug available for GBM, develops rapidly and frequently in patients...Hence, we developed an engineered nanoprogrammer using a metal-organic framework (MOF) coloaded with TMZ and the FAO inhibitor (etomoxir, ETO)...This dual-action strategy disrupted energy pathways in heterogeneous tumors, overcoming resistance. The nanoprogrammer demonstrated potent efficacy in orthotopic and patient-derived drug-resistant GBM models, achieving significant tumor suppression without notable toxicity."

Journal • Brain Cancer • Glioblastoma • Oncology • Oral Cancer • Solid Tumor

Long-chain fatty acids promote ATP production in post-thaw boar sperm through mitochondrial β-oxidation. (PubMed, Anim Reprod Sci) - "It was found that adding 100 μM mitochondrial β-oxidation inhibitor etomoxir to the extender, significantly reduced post-thaw boar sperm progressive motility, MMP, ATP levels, and CPT1 activity (P < 0.05), thereby attenuating the beneficial effects of exogenous LCFAs supplementation. These findings suggest that post-thaw boar sperm are capable of assimilating exogenous LFCAs, which subsequently promote mitochondrial β-oxidation, increasing TCA cycle activity and ATP production, therefore improving the quality of post-thaw boar sperm."

Journal

Fatty acid β-oxidation enhances immune regulatory function of double-negative T cells through pSTAT4-OX40 signaling pathway. (PubMed, Hepatol Commun) - "FAO regulates DNT cell survival and immunoregulatory function through the pSTAT4-OX40 pathway, enhancing their protective effect against autoimmune hepatitis."

IO biomarker • Journal • Autoimmune Hepatitis • Hepatitis C • Hepatology • Immunology • Inflammation • Liver Failure • CD4 • CD8

The ribonucleoprotein hnRNP K promotes hepatic steatosis by suppressing the nuclear hormone receptor PPARα. (PubMed, J Biol Chem) - "Etomoxir, an FAO inhibitor, counteracted the alleviation of lipid accumulation induced by hnRNP K knockdown. In summary, this study demonstrates hnRNP K has a crucial role in modulating the function of PPARα and hepatic lipid metabolism."

Journal • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • HNRNPK • PPARA

CPT1A mediated preservation of mitochondrial inhibits pyroptosis in pancreatic acinar cells. (PubMed, Front Cell Dev Biol) - "Cpt1a was knocked down (siRNA) or inhibited (etomoxir) in cells...These findings reveal a novel protective mechanism of CPT1A in SAP. Enhancing CPT1A activity preserves mitochondrial functions and suppresses NLRP3/GSDMD-mediated pancreatic acinar cell pyroptosis, highlighting CPT1A as a potential therapeutic target."

Journal • Metabolic Disorders • Pancreatitis • CPT1A • NLRP3

Altered fatty acid oxidation via CPT1A promotes epithelial-to-mesenchymal transition in ovarian cancer. (PubMed, FEBS J) - "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."

Journal • Oncology • Ovarian Cancer • Solid Tumor • CPT1A

Chemerin sustains the growth of spongiotrophoblast and sinusoidal trophoblast giant cells through fatty acid oxidation. (PubMed, BMC Biol) - "Our study demonstrated that chemerin-related lipid metabolism is crucial for EPC trophoblast differentiation during placental development, providing evidence that chemerin determines the growth of SpT and S-TGC through fatty acid oxidation. These findings also imply a possible pathological mechanism for pregnancy complications associated with chemerin."

Journal • Diabetes • Gestational Diabetes • Gynecology • Metabolic Disorders

PPAR-δ Orchestrates a Pro-metastatic Metabolic Response to Microenvironmental Cues in Pancreatic Cancer. (PubMed, Cancer Res) - "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."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MYC • PPARGC1A

SIRT2-dependent CPT1A deacetylation in macrophages inhibits periodontitis. (PubMed, Front Pharmacol) - "The anti-inflammatory effects of the CPT1A inhibitor Etomoxir (ETO) were assessed by qRT-PCR and Western blot analysis...Additionally, ChIP-qPCR further confirmed the interaction between Sirtuin-2 (SIRT2)-CPT1A, thereby impacting the acetylation levels of CPT1A and decreasing CPT1A activity. Overall, these findings demonstrate that SIRT2 binds to and deacetylates CPT1A, thereby inhibiting osteoclast differentiation and concurrently alleviating inflammation in periodontal tissues during experimental periodontitis progression."

Journal • Dental Disorders • Inflammation • Periodontitis • CPT1A • IL1B • IL6 • TNFA

Hypoxia-Driven Fatty Acid Metabolism Regulates Angiogenesis in Gastrointestinal Cancers (EACR 2025) - "We validated this negative tendency by using drugs blocking the FA oxidation (Etomoxir), the FA synthase (Denifanstat) or the FA uptake (Sulfosuccinimidyl oleate) and by administering increasing doses of palmitic acid. Our findings suggest that chronic hypoxia induces a metabolic shift in gastrointestinal cancer cells, leading to increased FA storage and secretion, which in turn modulates endothelial cell behavior and angiogenesis. The inverse correlation between secreted FA levels and vessel formation highlights a potential mechanism for aberrant tumor vascularization. Interestingly, gastric cancer cells appear to follow a distinct metabolic pattern, warranting further investigation."

Colon Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor

TARGETING FATTY ACID OXIDATION TO BOOST THE ANTITUMOR EFFECTS OF NUTRIENT STARVATION IN SOLID MALIGNANCIES (EACR 2025) - "To inhibit FAO, we used the Carnitine Palmitoyl transferase 1 inhibitors etomoxir or ST1326... FAO is a potential resistance mechanism to nutrient starvation. Combining FAOi with in vitro or in vivo starvation conditions results in cooperative antitumor effects that are mediated through the modulation of DNA repair and amino acid pathways. Our findings pave the way for conducting clinical trials to combine nutrient starvation approaches, such as FMD, with the modulation of FAO in combination with standard pharmacologic treatments."

Breast Cancer • Colorectal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

Mitochondrial metabolic rewiring drives wound healing in cystic fibrosis primary airway epithelium cultures treated with elexacaftor/tezacaftor/ivacaftor (ECFS 2025) - "The addition of the CPT1 inhibitor, Etomoxir, inhibited fatty acid oxidation and abolished the effect of ETI on wound healing. Our results suggest that ETI induces mitochondrial metabolic rewiring involving oxidative phosphorylation and fatty acid oxidation and that this participates in enhanced airway epithelium repair capacities highlighting a new role of CFTR in airway epithelial repair and metabolic pathways.1. Our results suggest that ETI induces mitochondrial metabolic rewiring involving oxidative phosphorylation and fatty acid oxidation and that this participates in enhanced airway epithelium repair capacities highlighting a new role of CFTR in airway epithelial repair and metabolic pathways.1. Crotta, S. et al. Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • PPARGC1A • TFAM