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

Molecular Characterization of PARP Inhibitor Response Reveals Co-Targeting Strategies in Advanced Prostate Cancer. (PubMed, Cancers (Basel)) - "Tumor cells exposed to longer-term treatment exhibit SLUG-dependent epithelial-mesenchymal transition (EMT) and evidence for altered fatty acid metabolism, both of which may be targeted to enhance PARPi anti-tumor cell effects. This study provides insight into both short and longer-term cellular response to PARPi treatment and provides a foundation for additional efforts to explore effective strategies to maximize the utility of PARP inhibition for managing prostate cancer."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • SNAI2

CPT1A through succinylation regulates the CTCF/LINC01503‒91aa feedback loop to promote gemcitabine resistance in pancreatic ductal adenocarcinoma. (PubMed, Clin Transl Med) - "We identified that LINC01503 is capable of encoding the protein product 1503-91aa. 1503-91aa competed with MCoA to unleash CPT1A activity for fatty acid oxidation and thereby mediating gemcitabine resistance in PDAC. Etomoxir and gemcitabine have synergistic effects in gemcitabine efficiency."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CPT1A

Numiera Therapeutics Awarded NCI Direct-To-Phase II SBIR Grant to Advance Etomoxir Into Clinical Trials for Glioblastoma (EIN News) - "NIH grant award of $2.3M will support clinical development of the company's orphan-designated first-in-class CPT1 inhibitor for the treatment of glioblastoma....This funding will support an early-phase clinical trial to evaluate the first-in-class CPT1 inhibitor etomoxir in the treatment of glioblastoma (GBM)."

Financing • New P2 trial • Glioblastoma

Propionyl-CoA catabolism is a metabolic gatekeeper for fatty acid oxidation in pancreatic cancer. (PubMed, Oncogene) - "Moreover, high PCCA expression in patient PDAC tumors is significantly associated with decreased lipid accumulation, and PDAC cells with high PCC levels are more sensitive to etomoxir-induced cell proliferation arrest. These findings establish the PCC-ACAA2 axis as a critical metabolic vulnerability and a promising target for diagnostic and therapeutic interventions in PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • PDX1

Long-chain fatty acid metabolism reprograms antitumor immunity: from molecular mechanisms to clinical translation. (PubMed, Biochem Pharmacol) - "AlphaFold3-predicted structures of CPT1A, ACSL4, ACSL5, FABP4, FABP5, and CD36 reveal deep hydrophobic pockets (Fpocket scores 0.67-0.81), and molecular docking maps inhibitor interactions: etomoxir (CPT1A His473 covalent), PRGL493 (ACSL4 AMP pocket), triacsin C (ACSL5 substrate tunnel), SBFI-26 (FABP5 β-barrel), and sulfo-N-succinimidyl oleate (CD36 SMAC pocket)...Accordingly, we assess translational strategies that target these metabolic nodes in a context-aware manner: context-dependent CPT1A inhibition or non-enzymatic activation; selective blockade of CD36 or FABP5; inhibition of oncogenic ACSL4; and complementary approaches harnessing ACSL4/5-mediated antitumor pathways (e.g., ferroptosis induction and antigen presentation enhancement) through tailored dietary interventions and combination therapies. This integrated structural, biochemical, and pharmacological framework highlights the necessity of uncoupling the opposing immunomodulatory roles of LCFAs using..."

Journal • Review • Oncology • ACSL4 • ACSL5 • CD36 • CD8 • CEBPB • CPT1A • FABP4 • FABP5 • IFNG • NLRC5 • PD-L1 • SCARB1 • SIRT6 • TFRC

Metformin Inhibits Cardiac Fibroblast Differentiation by Promoting Fatty Acid β-Oxidation: Implications for Age-Associated Cardiac Fibrosis. (PubMed, Cells) - "Importantly, inhibition of carnitine palmitoyltransferase-1 (CPT1) with etomoxir largely abolished the beneficial effects of metformin on mitochondrial respiration, fibroblast activation, and cellular senescence, demonstrating a critical role for FAO. These findings were corroborated in aged Apoe-/- mice, where metformin reduced the expression of cardiac fibroblast differentiation markers and enhanced FAO-associated markers. Collectively, our findings demonstrate that metformin suppresses cardiac fibroblast differentiation and senescence by preserving mitochondrial bioenergetics through FAO-dependent mechanisms, revealing a metabolic basis for its anti-fibrotic actions and supporting its therapeutic potential in age-related cardiovascular disease."

Journal • Cardiovascular • Fibrosis • Immunology • APOE • TGFB1

Inhibiting menin attenuates high-fat diet-induced weight gain by limiting intestinal lipid absorption in mice. (PubMed, J Clin Invest) - "Although lipid hydrolysis was enhanced, steady-state free fatty acid levels were not increased; instead, Men1 deficiency activated fatty acid β-oxidation programs and increased etomoxir-sensitive fatty acid-dependent mitochondrial respiration, supporting enhanced fatty acid catabolism...In a human gut organoid-on-chip system, MI-463 dose-dependently increased CES1 expression and markedly reduced lipid accumulation. Collectively, our findings identify menin as a regulator of intestinal lipid metabolism and suggest menin inhibition as a potential therapeutic strategy for obesity-related metabolic disorders."

Journal • Preclinical • Genetic Disorders • Metabolic Disorders • Obesity • APOB • CES1 • HDAC1

Ferroptosis-related biomarkers for diagnosis and mechanistic insights into Alzheimer's disease. (PubMed, Front Aging Neurosci) - "In addition, several candidate compounds, including etomoxir and tubastatin A, were predicted to potentially modulate these pathways. Three ferroptosis-related genes, NFKBIA, ATP6V1E1, and SUB1, were identified in Alzheimer's disease and showed consistent discriminative ability across multiple cohorts, with links to neuroinflammation, lysosomal function, and oxidative stress. These findings highlight their potential as candidate biomarkers warranting further investigation, although prospective validation in independent cohorts is required to confirm their diagnostic utility."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Inflammation • NFKBIA

Targeting a novel metabolic vulnerability of non-small cell lung cancer to fatty acid oxidation surmounts chemoresistance. (PubMed, Drug Resist Updat) - "Increased LAP:LIP ratio induced chemoresistance in NSCLC tumors by instigating a FAO-dependence, unveiling a metabolic vulnerability. FAO inhibition emerges as a novel chemosensitization strategy operating via rewiring tumor and TIME metabolism."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCB1 • ABCC1 • ABCC2 • CD34 • CPT1A

Mitochondrial dynamics: A promising tool for personalized TNBC management. (PubMed, Genes Dis) - "Mitochondrial energetics inhibitors, such as 2DG, 3BP, clotrimazole, and etomoxir, disrupt mitochondrial metabolic processes and reduce tumor growth in TNBC. This review highlights the latest advancements in mitochondrial dynamics and energetics in TNBC and explores the molecular mechanisms underlying their dysregulation. It also explores the therapeutic potential of targeting mitochondrial function for personalized strategies leading to improved clinical management of TNBC."

Journal • Review • Breast Cancer • CNS Disorders • Metabolic Disorders • Oncology • Psychiatry • Solid Tumor • Triple Negative Breast Cancer

Role of Fatty Acid Oxidation in Crohn's Disease and Ulcerative Colitis: Metabolomics Analysis and Experimental Evidence. (PubMed, Cell Biochem Funct) - "In vivo, the ability of butyrate to attenuate colitis and promote colonic iTreg accumulation was significantly reversed by the CPT1 inhibitor etomoxir. CPT1A-mediated fatty acid oxidation is a critical metabolic pivot through which butyrate signals to maintain immune tolerance. The systemic loss of FAO intermediates in CD patients directly contributes to impaired iTreg development, identifying the butyrate-CPT1A axis as a potential target for precision metabolic intervention."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • CD4 • CPT1A

miR-146a Mimic Therapy Protects Against Platelet-Mediated Thrombosis. (PubMed, Mol Ther) - "Platelet supplementation with palmitate or etomoxir, a Cpt1a inhibitor, increased or normalized miR-146a-/- platelets´ response, respectively, demonstrating that this deficiency enhanced fatty acid β-oxidation...In summary, our findings show that miR-146a deficiency leads to platelet hyperreactivity through metabolic reprogramming. Elevating miR-146a levels may be a therapy for preventing cardiovascular events."

Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Pneumonia • Respiratory Diseases • Thrombosis • CPT1A • MIR146A

Insulin Regulates CD36-Dependent Fatty Acid Uptake but Not Mitochondrial Oxidation in Sertoli Cells. (PubMed, Andrology) - "In the TM4 mouse SC line under defined in vitro conditions, insulin selectively regulates FA uptake while maintaining no control over downstream FA oxidation. This dissociation reveals that insulin modulates FA entry for storage and/or biosynthesis, while FA oxidation operates constitutively. Impaired FA uptake under insulin deficiency may compromise SC support for spermatogenesis, providing a mechanistic link to male infertility in DM that requires confirmation in primary SCs and in vivo diabetic models."

Journal • Diabetes • Infertility • Metabolic Disorders • Sexual Disorders • CD36 • CPT1A • SCARB1

Platelet ACKR3/CXCR7 Induced AMPKThr172-ACCSer79 pathway Regulates Procoagulant Functions: Implications for Immunothrombosis (ISTH 2026) - "However, unlike iloprost, which did not induce LC-CARs, anticoagulatory LC-CARs released from CXCR7-agonist-treated platelets reduced FXa-dependent thrombin generation, that was counteracted by CPT-1-inhibitor etomoxir. Conclusions Considering the regulatory impact of CXCR7-agonist on procoagulant platelet functions, besides 12-LOX Page 2 and Syk activities, therapeutic targeting of CXCR7 may modulate immunothrombotic complications arising from FcγRIIA-induced platelet activation, as encountered in HIT. Table or Figure Upload (1) ACKR3/CXCR7 induces anticoagulant acylcarnitines retarding FXa-driven thrombin generation, besides regulates Syk, 12-LOX and procoagulant functions, following platelet activation triggered by HIT-IgG DOI*10.1016/j.rpth.2026.103494"

Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Thrombosis • ACKR3 • ALOX15 • AMPK • SELP • SYK

Metabolic regulation-driven nanoparticles for tumor vulnerabilization and enhanced photodynamic therapy. (PubMed, J Control Release) - "The nanoplatform is constructed via the co-assembly of a disulfide-containing amphiphilic peptide and DSPE-PEG2k-FA, enabling the co-delivery of siRNA targeting monocarboxylate transporter 4 (siMCT4), the fatty acid β-oxidation (FAO) inhibitor Etomoxir, and chlorin e6 (Ce6)...In 4 T1 tumor-bearing mice, this combined disruption of lactate efflux and FAO, together with PDT, drove tumor cells into severe metabolic imbalance, leading to significant tumor growth inhibition. Collectively, this strategy provides a metabolism-oriented therapeutic approach to overcome tumor metabolic adaptability and enhance antitumor efficacy."

Journal • Oncology

Suppression of CPT1A-mediated Fatty Acid β-Oxidation Promotes Fibroblast Activation and Intestinal Fibrosis in Crohn's Disease (AOCC-IMKASID 2026) - "Activation of CPT1A with its agonist C75 markedly attenuated TGF-β-induced ECM production (Fig1I), whereas inhibiting FAO by etomoxir further exacerbated ECM production (Fig1J)... These findings identify suppression of CPT1A-mediated Fatty Acid β-Oxidation as a key metabolic reprogramming driving fibroblast activation and intestinal fibrosis in CD. Activation of CPT1A with the agonist C75 significantly alleviates fibrosis. Keywords: Intestinal Fibrosis, Fatty Acid Beta-Oxidation, CPT1A"

Crohn's disease • Fibrosis • Gastroenterology • Immunology • Inflammatory Bowel Disease • CPT1A • TGFB1

Energy substrate preference and metabolic flexibility in quiescent and oxytocin-stimulated human myometrial cells. (PubMed, iScience) - "In oxytocin-treated myometrial cells, this decrease was also observed upon BPTES treatment in addition to UK5099, suggesting that contractile myometrial cells can also utilize glutamine. Functionally, myometrial contractility was significantly reduced by UK5099 but not etomoxir, further indicating dependence on glucose utilization."

Journal • Hematological Disorders • Postpartum Hemorrhage

Lonicera japonica polysaccharide restores mucosal integrity in ulcerative colitis by increasing microbiota-derived spermidine. (PubMed, Cell Rep) - "Microbiota-derived spermidine interacts with HADHA and partially reverses inflammatory HADHA-associated metabolic reprogramming, as shown by restored fatty acid oxidation (FAO), reduced lactate accumulation, improved basal respiration and etomoxir-sensitive oxygen consumption rate (OCR), and preserved epithelial integrity in Caco-2 cells and intestinal organoids...Serum biochemical and protein analyses further support reduced systemic inflammation and improved mucosal homeostasis. These findings define a microbiota-derived spermidine-HADHA axis that supports mucosal homeostasis in ulcerative colitis."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Transplantation • Ulcerative Colitis

Spatiotemporal Targeting Randle Cycle and Immune Checkpoint for Potent Antitumor Therapy. (PubMed, Adv Sci (Weinh)) - "When combined with etomoxir (ETX), a fatty acid oxidation (FAO) inhibitor, this system effectively implements dual metabolic suppression, thereby enhancing reactive oxygen species (ROS)-induced immunogenic cell death and reprogramming the tumor immune microenvironment. Further combination with the immune checkpoint inhibitor αPD-1 amplified antitumor immune responses, achieving complete tumor regression in 60% of animals and full survival in 100% of tumor-bearing mice. This strategy demonstrates significant potential in the treatment of metastatic tumors through a synergistic starvation-oxidation-immunotherapy loop and paves the way for applying intratumorally-retaining nanogels to a broad spectrum of therapeutic proteins targeting metabolic pathways."

Journal • Head and Neck Cancer • Metabolic Disorders • Oncology • Oral Cancer • Solid Tumor

Deficiency of Serum Short-Chain Fatty Acid is Associated with Promoting Plasmablast Differentiation in Systemic Lupus Erythematosus (EULAR 2026) - "However, inhibition of fatty acid metabolism by etomoxir did not reverse SCFA- induced suppression of differentiation. Regarding HDAC inhibition, the HDAC inhibitor trichostatin A suppressed plasmablast differentiation when HDAC inhibition exceeded 30%...These findings suggest that reduced serum SCFA levels and impaired SCFA-GPR43 signalling in lupus patients may contribute to enhanced plasmablast differentiation. Fine-tuning of GPR43-mediated signalling may provide therapeutic insight for SLE."

Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • ARRB1 • IRF5 • NFKBIA • PRDM1 • TLR7 • TNFAIP3

Enhanced fatty acid availability rewires fibroblasts metabolism and decreases collagen deposition in lung fibrosis. (PubMed, Cell Mol Life Sci) - "This metabolic shift, but not the collagen reduction, was driven by increased fatty acid oxidation via CPT1, as confirmed by the use of the CPT1 inhibitor etomoxir. Importantly, in vivo metabolic interventions downregulated preferentially PDGFRα protein level, while in vitro provision of albumin-bound FA reduced both the amount of collagen produced by αSMA-positive cells and the amount of PDGFRα-positive cells, suggesting a dual role of FA on both pro-fibrotic fibroblasts. Collectively, our findings identify fatty acid oxidation as a potent metabolic checkpoint in fibrotic fibroblasts and support FA availability as a promising strategy to limit lung fibrosis progression."

Journal • Fibrosis • Immunology • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • PDGFRA • TGFB1

Scanning central carbon metabolism: a HILIC-HR-TOF-MS metabolome method. (PubMed, Metabolomics) - "Our HILIC-HR-TOF-MS metabolome method is efficient in mapping changes in metabolic intermediates of the CCM in mammalian cells. This approach holds potential for analysing a variety of biological samples across a range of applications, from drug development to biomedicine."

Journal

Zika Virus-Induced Metabolic Reprogramming Drives Lipid Droplet Biogenesis, Promoting Viral Replication and Ocular Pathogenesis. (PubMed, Cells) - "Modulation of FA metabolism further revealed differential effects on ZIKV infection: saturated FA (palmitate) enhanced viral replication, whereas inhibition of FA oxidation with etomoxir reduced infection...Collectively, these findings show that ZIKV reshapes host metabolic pathways in TM by differentially engaging AMPK signaling, FA metabolism, and LD biogenesis to promote viral replication and spread in ocular tissue. Targeting these metabolic pathways may offer promising therapeutic avenues for preventing and/or treating ZIKV-associated ocular complications."

Journal • Glaucoma • Infectious Disease • Metabolic Disorders • Ophthalmology • IFNAR1 • STK11

Differentiation stage of intestinal epithelial cells IPEC-J2 determines their metabolic response to lipid overload (ECO 2026) - "However, these cells didn't rely on FA oxidation as Cpt1b expression was reduced (-10%) and mitochondrial respiration was not affected by the inhibition of β-oxidation with etomoxir...These results stress out the need to develop interventions targeting undifferentiated intestinal epithelial cells to restore the energy metabolism of IECs and a normal systemic metabolism. Conflicts of Interest & Funding: No conflict of interest"

Genetic Disorders • Metabolic Disorders • Obesity • APOB • CLDN3 • CLDN7 • CPT1B • PCNA • PLIN2 • PPARA

TGM2-TUFM promotes acquired resistance to EGFR-TKIs in EGFR-mutated NSCLC through p62-mediated lipophagy. (PubMed, Respir Res) - "Our study revealed that TGM2 is a potential therapeutic target or biomarker for predicting acquired EGFR-TKI resistance in EGFR-mutated NSCLC."

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • GLS2 • PLIN2 • SQSTM1 • TGM2