BMS-345541 / BMS - LARVOL DELTA

Anti-proliferative and anti-inflammatory potential of 2-chloro-3-((4-hydroxyphenyl)amino)naphthalene-1,4-dione through targeting TNF-α/IL-8 and NF-κB signaling in HCT116 cancer cells: a comprehensive in silico docking and in vitro study. (PubMed, Biochem Biophys Rep) - "Molecular docking analysis demonstrated that the tested compound favorably interacted with key amino acid residues within human NF-κB/p50, the p50/p65 NF-κB complex, and IKKβ, with binding patterns to the active sites comparable to those of the reference inhibitors, MLN120B and BMS-345541...Collectively, these findings suggest that compound 12 exerts anticancer activity through dual anti-inflammatory and pro-apoptotic mechanisms, possibly by modulating the NF-κB pathway. This compound may therefore represent a promising lead candidate for further drug development against CRC."

Journal • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • CXCL8 • TNFA

The crosstalk between alternative splicing and histone ubiquitination modulates fast chemical reprogramming to pluripotency. (PubMed, Stem Cell Reports) - "Pharmacological inhibition of inflammatory pathway using Amlexanox and BMS-345541 could further improve FCR efficiency. Collectively, our results highlight the essential role of AS in FCR and suggest that the crosstalk between AS and histone ubiquitination mediated by PTBP3-SCMH1 axis can be harnessed for modulating cell fates. These studies will help to better understand the fascinating question of how small molecules alone can rapidly induce pluripotency and provide new approaches for regeneration and rejuvenation."

Journal • Targeted Protein Degradation • SCMH1

IPCEF1-Mediated NMDA Receptor Trafficking: A Novel IL-1β-Driven Mechanism Linking Inflammation to Epileptogenesis and NREM Sleep Desynchrony (EAN 2026) - "Interventions included IL-1 receptor antagonist (IL-1ra) and inhibitors of PIP3–AKT–NF-κB signalling (PIT-7, HS-173, BMS-345541)... IL-1β-driven IPCEF1-mediated NMDAR trafficking links inflammation to epileptogenesis and cortical desynchrony in NREM sleep. The IL-1-IPCEF1-NMDAR axis represents a precise therapeutic target for controlling seizures and sleep comorbidities in epilepsy. IL-1β-driven IPCEF1-mediated NMDAR trafficking links inflammation to epileptogenesis and cortical desynchrony in NREM sleep."

Epilepsy • Inflammation • Sleep Disorder • IL1B

Age-related bone loss inhibited by miR-146a is regulated via IRAK1 (EULAR 2026) - "Aged female miR-146a-deficient mice received 4-week treatments with NF-κB inhibitor (BMS-345541), JAK inhibitor (ruxolitinib), or dual JAK2/IRAK1 inhibitor (pacritinib), followed by histomorphometric bone density analysis. These mechanistic insights may enhance understanding of skeletal aging processes and osteoporosis pathogenesis, potentially informing therapeutic strategies for age-related bone disorders. Image(s), graphic(s), or table(s)"

Musculoskeletal Diseases • Orthopedics • Osteoporosis • CD4 • IFNG • IRAK1 • JAK2 • MIR146A • TRAF6

Age-related boneloss inhibited by miR-146a is regulated via IRAK1 (EWRR 2026) - "Aged female miR-146a-deficient mice received 4-week treatments with NF-κB inhibitor (BMS-345541), JAK inhibitor (ruxolitinib), or dual JAK2/IRAK1 inhibitor (pacritinib), followed by histomorphometric bone density analysis. These findings establish critical roles for IRAK1 and IFNγ in the pathogenesis of osteopetrosis in miR-146a-deficient mice. These mechanistic insights may enhance understanding of skeletal aging processes and osteoporosis pathogenesis, potentially informing therapeutic strategies for age-related bone disorders. Image 1"

Musculoskeletal Diseases • Orthopedics • Osteoporosis • CD4 • IFNG • IRAK1 • JAK2 • MIR146A • TRAF6

Leveraging drug-specific genes to identify sensitizers for resistant cancer cell lines. (PubMed, Cell Death Discov) - "The top-ranked compound was validated in resistant HeLa and NCI-H1299 cell lines using BMS-345541 and Vorinostat as primary agents. Our findings demonstrate that chaetocin can restore drug sensitivity in resistant cancer models, supporting its potential as a resistance-modulating agent in combination therapies. Given its epigenetic activity, chaetocin aligns with the emerging role of epigenetic modulators as promising partners in oncological co-treatments."

Journal • Preclinical • Oncology

Nfkb signaling in idecabtagene vicleucel infusion product drives response in relapsed/refractory multiple myeloma (ASH 2025) - "After manufacture, cells were treated for two hours with BMS-345541, a selective IKKβ inhibitor, or left untreated. This study presents the first scRNAseq analyses of ide-cel infusion product and elucidatesproduct specific factors that associate with efficacy in RRMM. NF-κB signaling, pro-survival genes, tonicsignaling signatures, and ide-cel construct expression in the ide-cel infusion product CD4 CAR-T cellswere significantly associated with improved depth and durability of responses. NF-κB signatures wereparticularly impactful and correlated with apheresis and TME T cells being more central memory-like andless exhausted."

IO biomarker • Hematological Malignancies • Multiple Myeloma • CCR7 • CD8 • ENTPD1 • IFNG • IL2 • IL6 • LAG3 • PD-1 • SDC1 • TIGIT • TNFA

Identification of Key Genes and miRNA-mRNA Regulatory Networks Associated with Intracranial Aneurysm Progression by Integrative Bioinformatics Analysis. (PubMed, Curr Med Chem) - "In summary, this study reveals some crucial genes and pathways potentially involved in the pathogenesis of IAs progression. These findings provide a new insight into the research and treatment of IAs."

Journal • Atherosclerosis • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage • Vascular Neurology • CCL2 • CCL20 • CD4 • CXCL1 • CXCL10 • CXCR2 • CXCR4 • IL6

Independent and synergistic roles of MEK-ERK1/2 and PKC pathways in regulating functional changes in vascular tissue following flow cessation. (PubMed, J Mol Cell Cardiol Plus) - "Rat basilar arteries were cultured for 48 h with selective inhibitors targeting MEK (Trametinib), PKC (RO-317549) and their downstream ERK (Ulixertinib) and NF-kB (BMS 345541). MEK inhibition is effective early, while PKC inhibition remains effective when applied later. The additive effects observed with combined MEK and PKC inhibition indicate parallel and functionally independent pathway activation during ETB receptor upregulation."

Journal • Cardiovascular

Activation of NF-?; B Promotes Distal Lung Organoid Formation (ATS 2025) - "Serum-free, feeder-free media was used, and organoids were cultured with and without IL-1β (for the first 3 days of culture), a small-molecule NF-κB inhibitor (BMS-345541), or vehicle throughout the duration of experiments... In conclusion, inhibiting NF-κB in distal lung epithelial progenitor cells led to decreased organoid formation. These findings suggest that NF-κB activation is important at initiating alveolar regeneration by promoting epithelial cell proliferation. Future studies will investigate the role of NF-κB in alveolar regeneration in vivo."

IL1B

CNPY2 modulates senescence-associated secretory phenotype in tendon stem/progenitor cells. (PubMed, Tissue Cell) - "Our findings showed that the NF-κB signaling pathway is activated in CNPY2 knockdown TSPCs, pharmacological inhibition of NF-κB signaling pathway with BMS-345541 attenuated SASP of senescent TSPCs, which indicated that CNPY2 regulates TSPCs SASP might through NF-κB signaling pathway. Our findings suggested that CNPY2 plays an important role in TSPCs senescence and SASP, CNPY2 could be a promising target for age-related tendon disorders."

Journal • Inflammation • CNPY2

Ischemic Insult Under Hyperhomocysteinemic Condition Triggers Early Onset Of Inflammatory Response Causing Exacerbation Of Brain Injury (ISC 2025) - "Inhibition of GluN2A-NMDAR (NVP-AAM077, i.v.) and NFκB (BMS345541, IKK inhibitor; i.p) at the onset of ischemic insult attenuated increase in MCP-1 mRNA and protein levels, as well as exacerbation of brain injury under hyperhomocysteinemic condition. The study provides compelling evidence for a novel role of GluN2A-NMDAR in promoting neuro-inflammatory response that contributes to exacerbation of stroke pathology under hyperhomocysteinemic condition."

Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Metabolic Disorders • Vascular Neurology • CCL2 • GRIN2A • GRIN2B

Estrogen receptor α regulates the IKKs/NF-kB activity involved in the development of mechanical allodynia induced by REM sleep deprivation in rats. (PubMed, Brain Res) - "Intrathecal administration of BMS-345541 or minocycline, two drugs that reduce the IKKs/NF-kB activity, avoided the development of mechanical allodynia in female but not in male rats subjected to 48 h of REMSD. Interestingly, ERα activation or ERα overexpression allowed the effect of BMS-345541 in male rats. Data suggest an important regulatory role of ERα in the IKKs/NF-kB activity on establishing mechanical allodynia induced by REMSD in female rats."

Journal • Preclinical • Pain • Sleep Disorder • ER

CCL25 contributes to the pathogenesis of D-Gal/LPS-induced acute liver failure. (PubMed, J Gastroenterol Hepatol) - "CCL25 contributes to ALF development by inducing macrophage-mediated inflammation via activation of the NF-κB signaling."

Journal • Hepatology • Inflammation • Liver Failure

BMS345541 is predicted as a repurposed drug for the treatment of TMZ-resistant Glioblastoma using target gene expression and virtual drug screening. (PubMed, Cancer Genet) - "Glioblastoma (GBM) is one of the most aggressive and fatal cancers, for which Temozolomide (TMZ) chemo drug is commonly used for its treatment. The ADMET analysis of this drug BMS345541 shows a higher half-life and lower cytotoxicity level than other predicted repurposed drugs. Hence, we conjecture that this could be a better drug for increasing the sensitivity of TMZ for treating GBM patients."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • FOXG1

Prognostic implication and immunotherapy response prediction of a novel ubiquitination-related gene signature in liver cancer. (PubMed, Aging (Albany NY)) - "In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC."

Gene Signature • IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • MCM10 • TRIM54

miR-146a-/- mice model reveals that NF-κB inhibition reverts inflammation-driven myelofibrosis-like phenotype. (PubMed, Am J Hematol) - "Furthermore, tailoring treatment with currently available JAK inhibitors (such as ruxolitinib or fedratinib) does not modify the natural history of the disease and has important limitations, including cytopenias...Specifically, we tested the JAK1/2 inhibitor, ruxolitinib; the NF-κB inhibitor via IKKα/β, BMS-345541; both inhibitors in combination; or a dual inhibitor of both pathways (JAK2/IRAK1), pacritinib...Additionally, combined treatment reduced both COL1A1 and IL-6 production in an in vitro model mimicking JAK2-driven fibrosis. In conclusion, NF-κB inhibition reduces, in vitro and in vivo, disease burden and BM fibrosis, which could provide benefits in myelofibrosis patients."

Journal • Preclinical • Hematological Disorders • Immunology • Inflammation • Myelofibrosis • Thrombocytopenia • COL1A1 • IL1B • IL6 • IRAK1 • MIR146A • TNFA

Calebin A modulates inflammatory and autophagy signals for the prevention and treatment of osteoarthritis. (PubMed, Front Immunol) - "To study the anti-degradative and anti-apoptotic effects of CA in an inflamed joint, an in vitro model of OA-EN was created and treated with antisense oligonucleotides targeting NF-κB (ASO-NF-κB), and IκB kinase (IKK) inhibitor (BMS-345541) or the autophagy inhibitor 3-methyladenine (3-MA) and/or CA to affect chondrocyte proliferation, degradation, apoptosis, and autophagy...However, the preventive properties of CA in OA-EN could be partially abrogated by the autophagy inhibitor 3-MA. The present results reveal for the first time that CA is able to ameliorate the progression of OA by modulating autophagy pathway, inhibiting inflammation and apoptosis in chondrocytes, suggesting that CA may be a novel therapeutic compound for OA."

Journal • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • BECN1 • MMP9 • mTOR • PI3K • SOX9 • TNFA

Low CDKN1B Expression Associated with Reduced CD8+ T Lymphocytes Predicts Poor Outcome in Breast Cancer in a Machine Learning Analysis. (PubMed, J Pers Med) - "In in vitro drug screening, BMS-345541 demonstrated efficacy as a therapeutic targeting of CDKN1B, effectively impeding the growth of breast cancer cells characterized by low CDKN1B expression. The inclusion of CDKN1B expression in GBM models increased the accuracy of survival predictions. CDKN1B expression plays a significant role in breast cancer progression, implying that targeting CDKN1B might be a promising strategy for treating breast cancer."

Biomarker • IO biomarker • Journal • Machine learning • Breast Cancer • Oncology • Solid Tumor • CD8 • CDKN1A • CDKN1B • CDKN2B

Repurposing of known drugs for COVID-19 using molecular docking and simulation analysis. (PubMed, Bioinformation) - "These top five compounds were boswellic acid, pimecrolimus, GYY-4137, BMS-345541 and triamcinolone hexacetonide that interacted with the chosen receptors 1R42, 4G3D, 6VW1, 6VXX and 7MEQ, respectively with binding energies of -9.2 kcal/mol, -9.1 kcal/mol, -10.3 kcal/mol, -10.1 kcal/mol and -8.7 kcal/mol, respectively. The MDS studies for the top 5 best complexes revealed binding features for the chosen receptor, human NF-kappa B transcription factor as an important drug target in COVID-19-based drug development strategies."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effects of Inhibition of IKK Kinase Phosphorylation On the Cellular Defence System and HSP90 Activity. (PubMed, Inflammation) - "In the A549 cells treated with BMS-345541 and LPS, COX2 activity is not induced: mRNA and protein levels have not increased, while there is an increase in the level of HSP90, HO1 proteins and mRNA. The results suggest that the IKK inhibition is effective in the reduction of the inflammatory response thanks to mechanisms involving both the heat shock cellular defense system and the antioxidative pathway."

Journal • Inflammation • HSP90AA1 • KEAP1

Comprehensive analysis of angiogenesis pattern and related immune landscape for individual treatment in osteosarcoma. (PubMed, NPJ Precis Oncol) - "OS patients with high ANGscore might be resistant to uprosertib, and be sensitive to VE821, AZD6738 and BMS.345541. In conclusion, we established a novel ANGscore system by comprehensively analysing the expression pattern of angiogenesis genes, which can accurately differentiate the prognosis and immune characteristics of OS populations. Additionally, the ANGscore can be used for patient stratification during immunotherapy, and guide individualized treatment strategies."

IO biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IFNG

NF-ΚB AND JAK/STAT PATHWAYS INHIBITION REVERSES FIBROSIS IN A MURINE MODEL OF INFLAMMATION-DRIVEN MYELOFIBROSIS (EHA 2023) - "Aims: To assess whether inhibition of NF-κB and/or JAK/STAT signaling can attenuate the inflammatory state and reverse the MF-like phenotype in an aged miR-146a -/- mouse model, using either (a) the JAK1/2 inhibitor ruxolitinib (RUX), (b) the NF-κB pathway inhibitor, through IKKα/β, BMS-345541 (BMS), (c) RUX+BMS, or (d) the dual JAK2/IRAK1 inhibitor pacritinib (PAC). In an aging-associated MF-like murine model without driver mutations, NF-κB inhibitors, either alone or incombination with JAK inhibitors, as well as dual-acting inhibitors, reduced inflammatory cytokines and splenomegaly, reversed thrombocytopenia and improved BM fibrosis. The combination therapy (RUX+BMS) produced BM aplasia and worsened anemia, whereas the dual inhibitor (PAC) improved or stabilized hematologic parameters. Bone Marrow Fibrosis, Myelofibrosis, NF- B, Myeloproliferative disorder"

Preclinical • Anemia • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • IL1B • IL6 • IRAK1 • ITGAM • MIR146A • NF-κβ • STAT5 • TNFA • TRAF6

IKKβ Inhibition Attenuates Epithelial Mesenchymal Transition of Human Stem Cell-Derived Retinal Pigment Epithelium. (PubMed, Cells) - "Further, we validated the effect of IKKβ inhibition on RPE-EMT-associated factors using a second IKKβ inhibitor, BMS345541, with RPE monolayers derived from an independent stem cell line. Our data highlights the fact that pharmacological inhibition of RPE-EMT restores RPE identity and may provide a promising approach for treating retinal diseases that involve RPE dedifferentiation and EMT."

Journal • Age-related Macular Degeneration • Diabetic Retinopathy • Macular Degeneration • Oncology • Ophthalmology • Retinal Disorders • NF-κβ • TGFB1 • TNFA

A Multi-Drug Tolerant Phenotype Is Induced By Diverse Microenvironmental Agonists in Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma (ASH 2018) - P1; "Responses to single-agent ibrutinib (IBR) or venetoclax (VEN) in Chronic Lymphocytic Leukemia (CLL) or Mantle Cell Lymphoma (MCL) are often incomplete suggesting drug combinations are needed to overcome de novo and acquired resistance...Using flow cytometric analysis of apoptosis, we noted tolerance to several pro-apoptotic agents (bendamustine, fludarabine, and inhibitors of Mcl-1, Bcl-xL, Bcl-2, and Bcl-2/Bcl-xL) including IBR+VEN in CD5+/19+cells from CLL samples treated with agonist mix, showing development of multi-drug tolerance in these cells...Consistently, multi-drug tolerance was rescued with inhibitors of NFkB (BMS345541 or Bortezomib) or drug combinations simultaneously inhibiting multiple anti-apoptotic proteins (inhibition of Mcl-1 with Bcl-2, Bcl-xL, or Bcl-2 and Bcl-xL)...Inhibitors of NFkB, or drug combinations targeting multiple pro-survival proteins, overcame multi-drug tolerance in agonist mix-treated samples and in CD69+CLL cells in patient PBMCs...

IO biomarker • Biosimilar • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Indolent Lymphoma • Inflammation • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology