BMS-536924 / BMS - LARVOL DELTA

Identification and validation of a diagnostic and prognostic model based on immune escape and cancer-associated fibroblast-related genes in lung adenocarcinoma. (PubMed, Medicine (Baltimore)) - "Kyoto Encyclopedia of Genes and Genomes analysis revealed pathways related to morphine addiction and protein digestion/absorption...Sensitivity to chemotherapeutics, such as AZD6482, ABT-263, A-770041, and BMS-536924, was observed in LUAD. Reverse transcription-quantitative polymerase chain reaction validation results demonstrated that KRT8 and S100A16 were significantly upregulated in tumor tissues, while COL4A3 and SMAD9 expression was downregulated, which was consistent with the TCGA-LUAD database analysis. In conclusion, 6 genes (KRT8, S100A16, COL4A3, SMAD9, MAP3K8, and CCDC146) were identified as potential biomarkers, offering valuable insights into LUAD pathogenesis and therapeutic strategies."

Biomarker • Journal • CNS Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Psychiatry • Solid Tumor • CD8 • MAP3K8 • S100A16 • SMAD9

IGF1-mediated mesenchymal-endothelial transition as a potential regulatory target in calcific aortic valve disease. (PubMed, BMC Med) - "We provide the first evidence that VICs have the capability to undergo endothelial transition under calcific conditions and that MEndT occurs in aortic valve of the CAVD mouse model. These findings reveal the presence of MEndT in CAVD, offering a potential therapeutic target."

Journal • Cardiovascular • CD31 • COL1A2 • IGF1 • PECAM1

Exploration of propionate metabolism-related genes to predict prognosis and immunotherapy response in ovarian cancer. (PubMed, J Ovarian Res) - "This study identified 5 biomarkers associated with the prognosis of OC, which might be helpful in understanding the roles of PMRGs in the development of OC in depth. The IHC validation provided additional evidence at the protein level, reinforcing the clinical relevance of these findings."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Oncology • Ovarian Cancer • Solid Tumor • EGR1 • GRIA1

Role of lysine acetylation-related genes in the diagnosis and prognosis of glioma. (PubMed, Sci Rep) - "Four drugs (PAC.1, OSI.906, WH.4.023, BMS.536924) were identified as chemotherapeutic drugs in Glioma. Finally, the expression of prognostic genes in tumor was significantly higher than that in normal tissue. New prognostic genes CD79B, STXBP4, DDHD1, FKBP1B, and TRAM2 were identified for glioma through the new perspective of lysine acetylation, suggesting their importance in the development of the disease and offering potential insights for diagnosis and treatment."

Journal • Brain Cancer • CNS Tumor • Developmental Disorders • Glioblastoma • Glioma • Oncology • Solid Tumor • CD79B

Identification of biomarkers associated with programmed cell death in liver ischemia-reperfusion injury: insights from machine learning frameworks and molecular docking in multiple cohorts. (PubMed, Front Med (Lausanne)) - "Finally, BMS-536924 and PF-431396 were identified as potential therapeutic agents for LIRI. This study comprehensively characterizes PCD in LIRI and identifies one core molecule, providing a new strategy for early prevention and treatment of LIRI."

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

Integrative analysis of a novel immunogenic PANoptosis‑related gene signature in diffuse large B-cell lymphoma for prognostication and therapeutic decision-making. (PubMed, Sci Rep) - "Additionally, the PANGPI enabled the identification of 3 chemotherapeutic agents, including BMS-536924, Gefitinib, Navitoclax for DLBCL patients in the high-risk group. We established a novel PANoptosis-related gene subtyping system in DLBCL, which could shed a novel light on the development of new biomarkers for DLBCL."

Biomarker • Gene Signature • IO biomarker • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Systematic Analysis of Disulfidptosis-Related lncRNAs in Hepatocellular Carcinoma with Vascular Invasion Revealed That AC131009.1 Can Promote HCC Invasion and Metastasis through Epithelial-Mesenchymal Transition. (PubMed, ACS Omega) - "Additionally, we identified valuable chemical drugs (AZD4547, BMS-536924, BPD-00008900, dasatinib, and YK-4-279) for high-risk VI+ HCC patients. Immunohistochemical analysis and hematoxylin-eosin staining (HE) staining provided preliminary evidence that AC131009.1 may promote the invasion and metastasis of HCC cells by inducing epithelial-mesenchymal transition (EMT) in both subcutaneous xenograft models and orthotopic HCC models within nude mice. To summarize, we developed a risk assessment model founded on DRLRs and explored the potential mechanisms by which hub DRLRs promote HCC invasion and metastasis."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • LUCAT1

SCHISTOSOMA MANSONI EGG ANTIGENS DRIVE HEPATIC AND COLONIC METABOLIC ACTIVITY VIA THE INSULIN/IGF-1R RECEPTOR (AASLD 2024) - "Mechanistic experiments using the insulin/IGF-1R inhibitor BMS 536924 revealed S. mansoni egg antigen-dependent activation of the insulin/IGF-1R signaling cascade including the activation of the proto-oncogene c-Jun... We demonstrated that S. mansoni soluble egg antigens cause the activation of insulin/IGF-1R signaling in murine and human hepatocytes and enterocytes which led to an inhibition of gluconeogenesis. Therefore, S. mansoni soluble egg antigens might improve insulin sensitivity. The activation of insulin/IGF-1R signaling could be a mechanism how the parasite eggs cover their energy supply from host cells."

Infectious Disease • AEBP1 • AKT3 • IGF1 • IGF2 • JUN • LEP • SERPINE1

Complement and coagulation cascades are associated with prognosis and the immune microenvironment of lower-grade glioma. (PubMed, Transl Cancer Res) - "By means of oncoPredict, MG-132, BMS-536924, PLX-4720, and AZD6482 were identified as potential sensitive drugs for high-risk patients, of which MG-132 was particularly recommended for high-risk patients. We performed in vitro experiments to explore the anti-glioma effect of MG-132, and the results demonstrated MG-132 could inhibit the proliferation and migration of glioma cells. Our findings show that CCC genes are associated with the prognosis and immune infiltration of LGG and provide possible immunotherapeutic and novel chemotherapeutic strategies for patients with LGG based on the risk signature."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • SERPINA1

Drug Repositioning of Inflammatory Bowel Disease Based on Co-Target Gene Expression Signature of Glucocorticoid Receptor and TET2. (PubMed, Biology (Basel)) - "BMS-536924 emerged as a top therapeutic candidate, and its validation experiment within the in vitro inflammatory model confirmed its efficacy in mitigating the LPS-induced inflammatory response. This study sheds light on the pathogenesis of IBD from a new perspective and may accelerate the development of novel therapeutic agents for inflammatory diseases including IBD."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • NR3C1 • TET1 • TET2

A novel telomere-related genes model for predicting prognosis and treatment responsiveness in diffuse large B-cell lymphoma. (PubMed, Aging (Albany NY)) - "Furthermore, high-risk DLBCL patients exhibited increased sensitivity to bortezomib, rapamycin, AZD6244, and BMS.536924, while low-risk DLBCL patients showed sensitivity to cisplatin and ABT.263. Using RT-qPCR, we found that three protective model genes, namely TCEAL7, EPHA4, and ELOVL4, were down-regulated in DLBCL tissues compared with control tissues. In conclusion, our novel TRGs-based model has great predictive value for the prognosis of DLBCL patients and provides a promising direction for treatment optimization."

IO biomarker • Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4 • EPHA4 • LAG3 • NCAM1 • PD-1 • PD-L1

PI3K pathway mutation predicts an activated immune microenvironment and better immunotherapeutic efficacy in head and neck squamous cell carcinoma. (PubMed, World J Surg Oncol) - "The PI3K pathway mutation status could be considered as a potential biomarker to predict better immunotherapeutic efficacy and clinical outcomes after immunotherapy in HNSC patients."

IO biomarker • Journal • Tumor mutational burden • Head and Neck Cancer • Immune Modulation • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TMB

Profiling of a novel circadian clock-related prognostic signature and its role in immune function and response to molecular targeted therapy in pancreatic cancer. (PubMed, Aging (Albany NY)) - "We successfully established and verified a novel circadian clock-related gene signature, which could stratify patients with different risk and be reflective of the therapeutic effect of molecular targeted therapy. Our findings could incorporate the pharmacological modulation of circadian clock into future therapeutic strategies."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ARNTL • CD8 • CDK1 • KLF10

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients. (PubMed, Front Genet) - "Patients with high HMAG scores were more suitable for the treatment of CHIR-99021, embelin, FTI-277, JNK-9L, JQ12, midostaurin, PF-562271, pyrimethamine, and thapsigargin, and patients with low HMAG scores were more suitable for the treatment of BMS-536924, CP466722, crizotinib, PHA-665752, rapamycin, and TAE684. We comprehensively evaluated the histone modification status in cervical cancer patients and revealed histone modification-associated prognostic genes to construct the HMAG signature, aiming to provide a new insight into prognosis prediction and precise clinical treatment."

Epigenetic controller • Journal • Cervical Cancer • Oncology • Solid Tumor

CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis. (PubMed, Mol Cancer) - "CircVAPA promotes SCLC progression via the miR-377-3p and miR-494-3p/IGF1R/AKT axis. We hope to develop clinical protocols of combinations of circVAPA inhibition and BMS-536924 addition for treating SCLC with circVAPA upregulation."

Journal • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • MIR494

Phenotypic Screening for Small Molecules that Protect β-Cells from Glucolipotoxicity. (PubMed, ACS Chem Biol) - "Validation studies in dissociated human islets identified 10 of the 17 compounds, namely, KD025, ETP-45658, BMS-536924, AT-9283, PF-03814735, torin-2, AZD5438, CP-640186, ETP-46464, and GSK2126458 that reduced glucolipotoxicity-induced β-cell death. These 10 compounds decreased markers of glucolipotoxicity including caspase activation, mitochondrial depolarization, and increased calcium flux. Together, these results provide a path forward toward identifying novel treatments to preserve β-cell viability in the face of glucolipotoxicity."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Neuroendocrine Tumor • Obesity • Solid Tumor • Type 2 Diabetes Mellitus

An Inflammatory Response Related Gene Signature Associated with Survival Outcome and Gemcitabine Response in Patients with Pancreatic Ductal Adenocarcinoma. (PubMed, Front Pharmacol) - "We found that the high-risk group had higher frequencies of KRAS, TP53, and CDKN2A mutations, increased infiltration of macrophages M0, neutrophils, and macrophages M2 cells, as well as upregulated hypoxia and glycolysis pathways, while the low-risk group had increased infiltration of CD8 T, naïve B, and plasma and macrophages M1 cells. We constructed and validated an IRRGs signature that could be used to predict the prognosis and gemcitabine response of patients with PDAC, as well as two drugs (BMS-536924 and dasatinib) may contribute to PDAC treatment."

Clinical • Journal • Inflammation • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD8 • CDKN2A • DCBLD2 • EREG • ITGA5 • KRAS • TP53

Targeting insulin receptor in estrogen receptor positive breast cancer (SABCS 2021) - "Previously our lab found that development of resistance to the commonly used ER-targeting drug tamoxifen (Tam) in vitro is associated with a loss of the type I IGF receptor expression with an increased dependence on the homologous insulin receptor (IR)...Interestingly, AKS130 induced IR downregulation was inhibited by pretreatment of BMS 536924, a dual IGF1R/IR kinase inhibitor...Addition of AKS-130 to Tam treatment trended toward delaying xenograft growth though further studies are needed, especially animal model systems of insulin resistance. These data indicate that IR signaling may represent a target to overcome or delay endocrine therapy resistance in breast cancer."

Breast Cancer • Colorectal Cancer • Estrogen Receptor Positive Breast Cancer • Gastrointestinal Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Oncology • Solid Tumor • ER • IR

Identification and initial characterization of a potent inhibitor of ferroptosis. (PubMed, J Cell Biochem) - "Instead, we provide evidence that BMS536924 binds iron, an essential cofactor in ferroptosis. Our results suggest caution in interpreting the effects of BMS536924 in investigations of insulin signaling and uncover a novel ferroptosis inhibitor."

Journal • Oncology • IR

ATM Mutations Benefit Bladder Cancer Patients Treated With Immune Checkpoint Inhibitors by Acting on the Tumor Immune Microenvironment. (PubMed, Front Genet) - "ATM mutations resulted in increased bladder cancer sensitivity to 29 drugs (P < 0.05), including cisplatin and BMS-536924, an IGF-1R inhibitor. Our results demonstrate the importance of ATM as a prognostic signature in bladder cancer and reveal that ATM may impact the effects of ICIs by acting on the tumor immune microenvironment."

Checkpoint inhibition • Clinical • IO Biomarker • Journal • Ataxia • Bladder Cancer • Genito-urinary Cancer • Immune Modulation • Immunology • Inflammation • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • Urothelial Cancer • ATM • TMB

The activation of an epithelial to mesenchymal transition program by insulin/insulin-like growth factor-1 receptors is involved in the acquired resistance to Anti-EGFR therapy of human cholangiocarcinoma cells (ILCA 2015) - Abstract #P-043; "Treatment of resistant pools with BMS-536924 reduced the expression of SNAIL, SLUG and ZEB-1 in the four cell lines. Moreover, co-treatment of CCA cells with erlotinib plus BMS-536924 was able to sensitize the resistant pools to erlotinib toxicity."

Preclinical • Oncology

IGF-1/insulin receptor kinase inhibition by BMS-536924 is better tolerated than alloxan-induced hypoinsulinemia and more effective than metformin in the treatment of experimental insulin responsive breast cancer (Endocr Relat Cancer) - Pharmacokinetic factors explain the tolerability of receptor inhibition relative to insulin deficiency, as the small molecule receptor kinase inhibitor BMS-536924 does not accumulate in muscle at levels sufficient to block insulin-stimulated glucose uptake

Preclinical-other • Breast Cancer • Oncology

BMS-536924, an ATP-competitive IGF-1R/IR inhibitor, decreases viability and migration of temozolomide-resistant glioma cells in vitro and suppresses tumor growth in vivo. (PubMed) - "This is the first report on anticancer activity of BMS-536924 in glioma. BMS-536924 is a promising compound in the therapy of glioma, especially of TMZ-resistant glioma, which might shed new light on glioma therapy."

Journal • Biosimilar • Oncology

Insulin-like growth factor binding proteins inhibit oocyte maturation of zebrafish. (PubMed, Gen Comp Endocrinol) - "Furthermore, we found the effect of NBI-31772 on oocyte maturation could be blocked by an Igf type 1 receptor inhibitor BMS-536924 in vitro, suggesting the Igfbps can inhibit the oocyte maturation via Igf/Igf1r pathway. Together, we provided the first evidence in fish that Igfbps inhibit oocyte maturation of zebrafish."

Journal