BMS309403 / BMS - LARVOL DELTA

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

Fatty acid binding protein 4 (FABP4) induces chondrocyte degeneration via activation of the NF-κb signaling pathway. (PubMed, FASEB J) - "In parallel, 24 6-week-old male C57/Bl6 mice were fed a high-fat diet (HFD) and randomly allocated to four groups: daily oral gavage with (1) PBS solution; (2) QNZ (NF-κB-specific inhibitor, 1 mg/kg/d); (3) BMS309403 (FABP4-specific inhibitor, 30 mg/kg/d); and (4) BMS309403 (30 mg/kg/d) + QNZ (1 mg/kg/d)...The use of QNZ and NF-κB-siRNA significantly alleviated the expression of catabolic markers of chondrocytes induced by FABP4. FABP4 induces chondrocyte degeneration by activating the NF-κB pathway."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • FABP4

Inhibition of Fatty Acid-Binding Protein 4 Protects Renal Tubular Epithelial Cells and Rescues Diabetic Kidney Disease (KIDNEY WEEK 2023) - "Mice were randomly assigned to receive an oral FABP4 inhibitor, BMS-309403, for 2 weeks. Administration of FABP4 inhibitor reduced the high glucose-induced apoptosis of renal proximal tubular epithelial cells... Taken together, inhibition of FABP4 could protect renal proximal tubular epithelial cells against the high glucose-induced damage in vitro and improve renal function, renal hypertrophy, and urinary albumin-to-creatinine ratios in DKD mice in vivo. Further molecular mechanistic insights may be explored to provide a novel theoretical basis for the potential therapeutic target of FABP4 in DKD."

Diabetes • Diabetic Nephropathy • Fibrosis • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Type 2 Diabetes Mellitus • FABP4 • IL1B • IL6 • TNFA

FABP4 mediates endoplasmic reticulum stress and autophagy to regulate endometrial epithelial cell function during early sheep gestation. (PubMed, J Reprod Dev) - "Moreover, the FABP4 inhibitor BMS309403 counteracted hormone-mediated functional changes in SEECs, and an endoplasmic reticulum stress activator and autophagy inhibitor reversed the abnormal secretion of prostaglandins induced by FABP4 inhibition. These results suggest that FABP4 affects ovine endometrial function during early gestation by regulating endoplasmic reticulum stress and autophagy in SEECs."

Journal • FABP4

Fatty Acid-Binding Protein 4 is Essential for the Inflammatory and Metabolic Response of Microglia to Lipopolysaccharide. (PubMed, J Neuroimmune Pharmacol) - "LPS-stimulated BV-2 microglia demonstrated a significant increase in the production of reactive oxygen species (ROS) and tumour necrosis factor-alpha (TNF-α), phosphorylation of c-Jun N-terminal kinase (JNK), increased expression of Toll-like receptor 4 (TLR4), and reduced expression of uncoupling protein 2 (UCP2), all of which were reversed following FABP4 genetic silencing and chemical inhibition with BMS309403. The oxidation rate of H-oleic acid and microglial uptake of H-2-deoxy-D-glucose were modulated with LPS activation, processes which were restored with genetic and chemical inhibition of FABP4. This is the first study to report on the critical role of FABP4 in mediating the deleterious effects of LPS on microglial immunometabolism, suggesting that FABP4 may present as a novel therapeutic target to alleviate microglia-mediated neuroinflammation, a commonly reported factor in multiple neurodegenerative diseases."

IO biomarker • Journal • CNS Disorders • Inflammation • Oncology • FABP4 • MAPK8 • TLR4 • TNFA

FATTY ACID BINDING PROTEINS (FABPS) INHIBITION IMPAIRS METABOLIC HOMEOSTASIS IN RENAL TUBULAR CELLS. (ERA-EDTA 2023) - "Mitochondrial redox status, proliferation, death rate, and fatty acid oxidation (FAO) were studied in renal tubular cells in conditions of overall FABP inhibition with BMS309403... In brief, FABP inhibition disrupts tubular energetic status and favours cell stress. Thus, protecting FABP activity could help to preserve tubular metabolic homeostasis during early kidney damage."

Renal Disease • AMPK

Adipocyte-derived FABP4 promotes non-alcoholic fatty liver disease (NAFLD)-induced hepatocellular carcinoma by driving Wnt/β-catenin signaling cascade (EACR 2023) - "HCC cells pre-incubated with conditioned medium (CM) of adipocytes showed enhanced liver CSC properties including self-renewal, tumorgenicity, invasiveness and chemo-resistance to doxorubicin and sorafenib...Concurrently, rrecombinant FABP4 enhanced CSC properties of HCC cells; while FABP4 inhibitor (BMS309403) abolished the CSC enhancing effect of adipocytes CM...ConclusionAdipocyte-derived FABP4 may crucial role in development of NAFLD-induced HCC. Targeting the adipocyte-derived, FABP4-mediated PI3/Akt/ β-catenin cascade may be a therapeutic strategy for the treatment of this disease."

Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Non-alcoholic Fatty Liver Disease • Oncology • Solid Tumor • FABP4

Targeting the fatty acid binding proteins disrupts multiple myeloma cell cycle progression and MYC signaling. (PubMed, Elife) - "Myeloma cell responses to BMS309403, SBFI-26, or both, were also assessed with RNA sequencing (RNA-Seq) and proteomic analysis, and confirmed with western blotting and qRT-PCR...In MM cells, FABPs have a multitude of actions and cellular roles that result in the support of myeloma progression. Further research into the FABP family in MM is warrented, especially into the effective translation of targeting these in vivo."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • FABP5 • MYC