BMS309403 / BMS - LARVOL DELTA

Molecular mechanisms underlying fetal bovine serum-induced developmental delay in mouse embryos: a data-independent acquisition (DIA)-based proteomics study. (PubMed, Front Mol Biosci) - "At a concentration of 200 nm, the FABP4 inhibitor BMS-309403 can cause embryonic retardation and increase the levels of ROS...Furthermore, proteomic analysis revealed that FABP4 is regulated by an integrated cytoskeleton-nuclear-cytoplasmic transport-metabolic network. The inhibition of FABP4 led to the retardation of embryonic development and increased the levels of ROS."

Journal • Preclinical • Developmental Disorders • Metabolic Disorders • FABP4 • KPNA2 • KPNB1

Novel Aspects of Fatty Acid-Binding Protein 4 in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis (ERA 2026) - "Furthermore, FABP4 inhibition by BMS309403 ameliorated renal injury in a rat mole of ANCA-GN. Conclusion Urinary FABP4 was a potential noninvasive biomarker of disease activity and severity in ANCA-GN, and FABP4 might act as a promising therapeutic target against ANCA-GN."

Glomerulonephritis • Inflammation • Lupus Nephritis • Metabolic Disorders • Nephrology • Vasculitis • FABP4

A novel mechanism by which the FABP4/CD36 axis exacerbates cholestasis via antagonizing FXR signaling (EASL 2026) - " We used a multidisciplinary approach (genetic: Fxr-deficient mice; pharmacological: FABP4 inhibitor BMS309403) to induce cholestasis with alpha-naphthylisothiocyanate (ANIT)... This study confirms macrophage-derived FABP4 is a key upstream FXR signaling suppressor in cholestatic liver disease. It drives cholestatic injury by blocking this core hepatoprotective pathway, causing uncontrolled BA toxicity. We reveal a novel immune-metabolic circuit (FABP4/CD36 to FXR) and validate FABP4 as a potential target for restoring BA homeostasis in cholestasis."

Cholestasis • Hepatology • Inflammation • Liver Failure • CD36 • CYP8B1 • FABP4 • SCARB1

Pharmacological Inhibition of Fatty Acid-Binding Protein 4 Alleviates Sepsis-Associated Acute Kidney Injury in Mice via Suppressing Ferroptosis. (PubMed, Eur J Pharmacol) - "To explore the functional role of FABP4, we administered BMS-309403 (BMS), a selective FABP4 inhibitor, in both a lipopolysaccharide (LPS)-induced murine SA-AKI model and an in vitro model of RAS-selective lethal 3 (RSL3)-treated human renal tubular epithelial (HK-2) cells...Furthermore, in vitro experiments confirmed that BMS effectively mitigated RSL3-induced ferroptosis in HK-2 cells. To our knowledge, this study is the first to demonstrate that FABP4 exacerbates SA-AKI by promoting ferroptosis, suggesting that targeted inhibition of FABP4 may represent a promising novel therapeutic strategy for SA-AKI."

Journal • Preclinical • Acute Kidney Injury • Infectious Disease • Inflammation • Nephrology • Renal Disease • Septic Shock • ACSL4 • FABP4 • GPX4

Oleic Acid Fuels Cisplatin-Resistant Ovarian Cancer Through FABP4-Driven Lipid Uptake. (PubMed, Mol Metab) - "Pt-R OC cells harbor heightened dependence on unsaturated FAs compared to Pt-S cells and upregulate key transporters to increase FAs uptake. OA supports the proliferation of Pt-R cells in vitro and in vivo and a combination of carboplatin and FABP4 inhibitor reduces OC growth in vivo. These findings suggest that lipid composition may influence therapeutic response and raise important considerations for dietary guidance in patients with cancer."

Journal • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor • CD36 • E2F1 • FABP4 • SCARB1

Fatty acid uptake mediated by FABP4 promotes the formation of CD8+T cell senescence through lipid peroxidation in the adipocyte-rich microenvironment of Ovarian Cancer. (PubMed, Oncogenesis) - "Moreover, using an OvCa mouse model, we found that in OvCa mice BMS309403 treatment partially diminished CD8+Tsen formation by reducing FA uptake, and improved anti-tumor immunity, and prolonged the survival time of OvCa mice when combined with chemotherapy. Our work suggests FABP4-mediated FA metabolism as a therapeutic target to counteract T cell senescence in adipocyte-rich TME, providing a novel immunotherapeutic strategy for OvCa."

Journal • Oncology • Ovarian Cancer • Solid Tumor • FABP4

Fatty acid binding protein 4 induces osteogenesis and angiogenesis as pathogenesis of metabolic osteoarthritis. (PubMed, Mol Med) - "This study suggests that FABP4 induced subchondral bone osteogenesis and angiogenesis. The PI3K-Akt signaling pathway plays a critical role in both processes. Inhibition of FABP4 may serve as a potential therapeutic approach for metabolic OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • FABP4

Fatty Acid-binding Protein 4 Exacerbates Blood-brain Barrier Disruption Through the JNK/c-Jun/MMP12 Pathway After Traumatic Brain Injury. (PubMed, Mol Neurobiol) - "This study investigates the molecular mechanisms by which FABP4 regulates BBB disruption following TBI and evaluates the therapeutic potential of the selective FABP4 inhibitor BMS309403 in TBI pathology...FABP4 exacerbates BBB disruption after TBI via the JNK/c-Jun/MMP12 pathway. Inhibition of FABP4 offers a potential therapeutic strategy for improving TBI outcomes."

Journal • CNS Disorders • Vascular Neurology • FABP4

Inhibition of Fatty Acid-Binding Protein 4 Limits High-Fat-Diet-Associated Prostate Tumorigenesis and Progression in TRAMP Mice. (PubMed, Int J Mol Sci) - "Additionally, treatment with BMS309403-a chemical inhibitor of FABP4-was observed to abrogate the HF-mediated TRAMP tumor progression, along with reductions in body weight and cytokine production. Thus, FABP4 plays an essential role in the progression of HF-mediated prostate cancer through the modulation of metabolic and inflammatory pathways, providing a potential therapeutic target for prostate cancer."

Journal • Preclinical • Genetic Disorders • Genito-urinary Cancer • Obesity • Oncology • Prostate Cancer • Solid Tumor • FABP4

Novel Aspects of Fatty Acid-Binding Protein 4 in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis (KIDNEY WEEK 2025) - "Furthermore, FABP4 inhibition by BMS309403 ameliorated renal injury in a rat mole of ANCA-GN. Conclusion Urinary FABP4 was a potential noninvasive biomarker of disease activity and severity in ANCA-GN, and FABP4 might act as a promising therapeutic target against ANCA-GN."

Glomerulonephritis • Immunology • Inflammation • Lupus Nephritis • Metabolic Disorders • Nephrology • Renal Disease • Vasculitis • FABP4

Fatty Acid Binding Protein 6 (FABP6) Represents a Novel Target for Multiple Myeloma (ASH 2024) - "The TRIPZshRNA inducible lentivirus expression system containing a red fluorescent protein (RFP) reporter was used to generate stable, doxycycline (DOX)-inducible cells with knockdowns as follow : FABP5 (shFABP5), FABP6 (using 3 different shRNAs : shFABP6/58 shFABP6/59, and shFABP6/61), or non-targeting controls (NC)...In both cohorts, bioluminescent imaging (BLI) analysis revealed significantly lower tumor burden in BMS309403-treated versus vehicle-treated mice. MMCLs with FABP6 and FABP5 KD will next be assessed in vivo. Taken together, in vitro, in vivo, and patient data all suggest that FABP5 and FABP6 are novel targets in MM and suggest that FA metabolism is a newly-identified vulnerability that should be exploited for MM therapy."

Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • Oncology • Solid Tumor • FABP3 • FABP4 • FABP5 • FABP6 • SDC1

An etiology-stratified single-cell atlas identifies FABP4 as a prognostic marker for MASLD-related HCC. (PubMed, J Hepatol) - "These findings reveal etiology-heterogeneous immune landscapes in HCC and identify FABP4 as a potential prognostic biomarker to guide immunotherapy in MASLD-related HCC."

Biomarker • IO biomarker • Journal • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • CD8 • FABP4 • NOTCH1 • PPARG

Age-associated T cell immunity decreases circulating endothelial progenitor cells. (PubMed, Stem Cells) - "Importantly, treatment with FABP4 in bone marrow cells increased inhibitory T cells while decreased SDF-1 receptor, CXCR4 in EPCs, whereas blocking FABP4 signaling by BMS309403 or depleting these T cells restored surface expression of CXCR4 in EPCs. Notably, FABP4-mediated decrease of circulating EPC in aging were restored by therapeutic administration of mitochondria, wherein plasma FABP4 was decreased along with reducing inhibitory T cell induction in bone marrow and increasing circulating EPCs in older mice. Collectively, these findings provide new insight into the involvement of age-associated T cell immunity in EPC dysregulation, and FABP4 may be a therapeutic target to detain vascular aging."

Journal • CXCL12 • CXCR4 • FABP4

FABP5 reprograms lipid metabolism and promotes cutaneous T-cell lymphoma progression via activation of PPARγ signalling. (PubMed, Indian J Dermatol Venereol Leprol) - "In addition, the precise molecular interactions between FABP5 and PPARγ signalling in CTCL remain unclear. Conclusion Our findings suggest that the FABP5/PPARγ axis is a promising therapeutic target in CTCL, with BMS-309403 emerging as a potential agent to reverse lipid metabolic reprogramming in CTCL."

Journal • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Metabolic Disorders • Mycosis Fungoides • Oncology • Skin Cancer • T Cell Non-Hodgkin Lymphoma • CDH1 • CDH2 • FABP5 • FASN • PPARG

FABP4 Inhibitor Improves Right Ventricular Fibrosis in Metabolic Syndrome- Related Pulmonary Hypertension due to Left Heart Disease in Mice. (PubMed, FASEB J) - "Treatment with the FABP4 inhibitor BMS309403 (BMS) significantly reduced MetS-related comorbidities, improved hemodynamics, and alleviated cardiac dysfunction, pulmonary vascular remodeling, myocardial hypertrophy, and fibrosis...These findings demonstrate that FABP4 serves as both a potential plasma biomarker for PH-LHD severity and a therapeutic target. BMS ameliorates PH-LHD by inhibiting RV fibrosis via modulation of CF differentiation into myofibroblasts, underscoring FABP4 as a promising intervention for PH-LHD."

Journal • Preclinical • Cardiovascular • Fibrosis • Heart Failure • Hypertension • Immunology • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • FABP4 • SMAD3

FABP4 inhibition suppresses bone resorption and protects against postmenopausal osteoporosis in ovariectomized mice. (PubMed, Nat Commun) - "Notably, bone-targeted delivery of BMS309403 achieves comparable efficacy to alendronate. In this work, we demonstrate that FABP4 is a critical mediator in PMOP and that its inhibition offers a promising therapeutic strategy."

Journal • Preclinical • Inflammation • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • FABP4 • NFATC1

FABP4-mediated ERK phosphorylation promotes renal cancer cell migration. (PubMed, BMC Cancer) - "To assess the effects of adipocyte-released FABP-4, on cancer malignant phenotype we evaluated 786-O and ACHN proliferation and migration, using Ad-CM from ccRCC and Ad-CM from HD alone or in combination with FABP4 inhibitor BMS309403...Moreover, in both cell lines, FABP4 effect was associated with an increased ERK phosphorylation. Collectively these data support the role of FABP4 in ccRCC progression and its potential use as noninvasive biomarker and therapeutic target for ccRCC."

Journal • Clear Cell Carcinoma • Clear Cell Renal Cell Carcinoma • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • FABP4

Identification of Fatty Acid-Binding Protein 4 as a Potential Biomarker and Therapeutic Target for Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis. (PubMed, Kidney Dis (Basel)) - "Furthermore, FABP4 inhibition by BMS309403 ameliorated renal injury in a rat mole of ANCA-GN. Urinary FABP4 levels might reflect the disease activity and renal involvement of ANCA-associated vasculitis, and FABP4 might act as a promising therapeutic target against ANCA-GN."

Biomarker • Journal • Acute Kidney Injury • ANCA Vasculitis • Glomerulonephritis • Immunology • Lupus Nephritis • Nephrology • Renal Disease • Vasculitis • FABP4

Effects of pharmacological inhibition of FABP4 during gestation and lactation on offspring neurodevelopment and behavior. (PubMed, Neurosci Lett) - "These findings suggest that FABP4 inhibition during the perinatal period perturbs lipid metabolism and may influence neurodevelopment through systemic metabolic changes. Although the direct effects of BMS309403 on the fetal brain cannot be excluded, alteration in maternal metabolism and placental function may have contributed to the observed neurodevelopmental changes in offspring."

Journal • Autism Spectrum Disorder • CNS Disorders • Depression • Developmental Disorders • Genetic Disorders • Inflammation • Metabolic Disorders • Psychiatry • Solid Tumor • FABP4 • IL10 • IL12A • TNFA

Fatty acid binding protein 4 regulates doxorubicin-induced renal injury via mediating lipid metabolism and apoptosis. (PubMed, Chem Biol Interact) - "In vitro experiment, HK-2 cell was used to detect DOX-induced kidney cell injury with or without BMS309403. FABP4 mediated DOX induced kidney damage in normal mice and tumor-bearing mice by lipid metabolism disorders and cell apoptosis. This study may enhance the clinical management of DOX-induced kidney injury and provide new therapeutic targets and preventive strategies for the clinical application of DOX."

Journal • Dyslipidemia • Metabolic Disorders • Nephrology • Oncology • Renal Disease • FABP4

Targeting FABP4/UCP2 axis to overcome cetuximab resistance in obesity-driven CRC with drug-tolerant persister cells. (PubMed, Transl Oncol) - "In vivo, the FABP4 inhibitor BMS309403, either alone or in combination with cetuximab, significantly reduced tumor growth in resistant CRC models, highlighting its therapeutic potential. These findings establish the FABP4/UCP2 axis as a pivotal driver of cetuximab resistance in obesity-associated CRC and suggest that targeting this metabolic pathway could improve outcomes in DTP-resistant CRC patients."

Journal • Colorectal Cancer • Genetic Disorders • Obesity • Oncology • Solid Tumor • FABP4

Gut microbiota-derived acetic acids promoted sepsis-induced acute respiratory distress syndrome by delaying neutrophil apoptosis through FABP4. (PubMed, Cell Mol Life Sci) - "Then, FABP4 inhibitor BMS309403 was used to treat neutrophils...Moreover, FABP4 in neutrophils regulated the injury of RLE-6TN through inflammatory factors. In conclusion, FABP4 affected by gut microbiota-derived SCFAs delayed neutrophil apoptosis through ER stress, leading to increased inflammatory factors mediating lung epithelial cell damage."

Journal • Acute Respiratory Distress Syndrome • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Septic Shock • CCL3 • FABP4 • IFNG • IL1B • IL6 • TNFA

A Nanocapsule System Combats Aging by Inhibiting Age-Related Angiogenesis Deficiency and Glucolipid Metabolism Disorders. (PubMed, ACS Nano) - "Here, we constructed a Pd/hCeO2-BMS309403@platelet membrane (PCBP) nanoheterostructured capsule system loaded with fatty acid-binding protein 4 (FABP4) inhibitors and modified with platelet membranes and investigated its therapeutic role in aged mice...In senescent ECs, PCBP mediated the activation of vascular endothelial growth factor (VEGF) signaling and glycolysis and inhibition of FABP4 by inducing the synthesis of hypoxia-inducible factor-1α, thereby reawakening neovascularization and restoring glycolipid metabolic homeostasis. In conclusion, the PCBP nanocapsule system provides a promising avenue for interventions against aging-induced dysfunction."

Journal • Dyslipidemia • Inflammation • Metabolic Disorders • FABP4 • HIF1A

FABP4 Is an Indispensable Factor for Regulating Cellular Metabolic Functions of the Human Retinal Choroid. (PubMed, Bioengineering (Basel)) - "Using four representative intraocular tissue-derived cell types, including human non-pigmented ciliary epithelium (HNPCE) cells, retinoblastoma (RB) cells, adult retinal pigment epithelial19 (ARPE19) cells and human ocular choroidal fibroblast (HOCF) cells, the intraocular origins of FABP4 were determined by qPCR analysis, and the intracellular functions of FABP4 were investigated by seahorse cellular metabolic measurements and RNA sequencing analysis using a specific inhibitor for FABP4, BMS309403...Furthermore, upstream analysis using IPA suggested that NKX2-1 (thyroid transcription factor1), HOXA10 (homeobox A10), GATA2 (gata2 protein), and CCAAT enhancer-binding protein A (CEBPA) were upstream regulators and that NKX homeobox-1 (NKX2-1), SFRP1 (Secreted frizzled-related protein 1) and TREM2 (triggering receptor expressed on myeloid cells 2) were causal network master regulators. The findings in this study suggest that intraocularly present FABP4 originates from the..."

Journal • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • CEBPA • FABP4 • GATA2 • HOXA10 • NKX2-1 • SFRP1

Integrated multi-omic analysis identifies fatty acid binding protein 4 as a biomarker and therapeutic target of ischemia-reperfusion injury in steatotic liver transplantation. (PubMed, Cell Mol Life Sci) - "FABP4 was identified as a hypoxia-inducible protein that sensitized steatotic liver grafts to IR injury. The FABP4 inhibitor, BMS-309403, could activate of cAMP signaling pathway thereby modulating mitochondrial membrane homeostasis, reducing oxidative stress injury in steatotic donors."

Biomarker • Journal • Cardiovascular • Hepatology • Liver Failure • Reperfusion Injury • Transplantation • FABP4