BAY 872243 / Bayer - LARVOL DELTA

Tumor neutrophils mediate immunosuppression through the hypoxia-EGR1-PTGS2 signaling axis in advanced head and neck carcinomas unrelated to HPV (AHNS 2026) - "Here, using DMSO-differentiated HL60 cells as a model for human neutrophils, we show that hypoxia-induced EGR1 expression is reduced in the presence of the IRE-1/ER stress inhibitor B-I09 or the MEK1/2 inhibitor trametinib but not reduced in the presence of the HIF1 inhibitor BAY87-2243 or the HIF2 inhibitor PT2399...Importantly, immunosuppressive function of human peripheral blood neutrophils exposed to hypoxia was abrogated in the presence of celecoxib (COX2 inhibitor) but not OSM or IL-1b neutralization, confirming the role of PGE2 in hypoxic neutrophil immunosuppression...Together, these data indicate that tumor neutrophils immunosuppress T cell function through the function of COX2 and downstream production of PGE2 and that this pathway can be abrogated with MAPK-pathway inhibition, possibly resulting in enhanced response to immunotherapy. This data informs neoadjuvant combination immunotherapy studies in patients with advanced head and neck carcinomas that aim to..."

IO biomarker • Metastases • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • EGR1 • ERN1 • HIF1A • IL1B • PACERR • PTGS2

Ginsenoside-Rh2 Alleviates Pyroptosis of Nucleus Pulposus Cells by Activating Autophagy via HIF-1α to Retard the Progression of Intervertebral Disc Degeneration. (PubMed, J Cell Physiol) - "In rat IVDD models, GRh2 maintained disc structural stability and extracellular matrix homeostasis, while BAY872243 reversed this protective effect. In conclusion, GRh2 alleviates IVDD by activating autophagy mediated by HIF-1α, as well as inhibiting pyroptosis and extracellular matrix damage, making it a potential therapeutic agent for IVDD."

Journal • HIF1A • IL1B

HIF1α mediates resistance to radiation and to KRAS inhibitors in pancreatic adenocarcinoma. (PubMed, PLoS One) - "To explore this, we conducted a drug repurposing screen and identified three HIF1α inhibitors (bakuchiol, BAY-87-2243, 2-methoxyestradiol) whose sensitivities were correlated with sensitivity to Deltarasin, a KRAS inhibitor. Our findings suggest that HIF1α inhibitors could be used to sensitize PDAC to radiotherapy and KRAS inhibitors."

Journal • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • HIF1A • KRAS

A Biomimetic Micro-Nano System Maximizing 'Active Transport and Retention' Effect in Solid Tumors. (PubMed, Small) - "PG@BAM-LRC loaded with BAY-872243 exhibits exceptional tumor accumulation and therapeutic outcome compared to LRC, PG@LRC without BAM, and PG@BAM-LRC. Collectively, this study establishes PG@BAM-LRC as a robust tumor-targeting system leveraging the ATR mechanism while addressing tumor heterogeneity."

Journal • Oncology • Pancreatic Cancer • Solid Tumor • MMP9

GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury. (PubMed, Front Immunol) - "Using LPS-challenged mouse endotoxemia and a murine macrophage (RAW264.7) cell line model, we assessed GDF15's functional role through: (1) recombinant Adeno-Associated Virus serotype 8 (rAAV8)-mediated tissue-specific overexpression, (2) siRNA knockdown, (3) pharmacological modulation (BAY 87-2243/Hypoxia-Inducible Factor 1-alpha (HIF-1α) inhibitor, Shikonin/PKM2 inhibitor, Asiaticoside/SMAD7 activator), and (4) comprehensive metabolic-inflammatory phenotyping including mitochondrial complex integrity (assessed via UQCRC1, Ubiquinol-Cytochrome c Reductase Core Protein 1), cytokine dynamics (TNF-α, IL-6) and lactate metabolism...GDF15 orchestrates sepsis tolerance through the SMAD7-HIF-1α axis, preserving mitochondrial integrity while resolving metabolic-inflammatory dysregulation, notably by suppressing the release of pro-inflammatory cytokines such as TNF-α and IL-6. This study identifies GDF15 as a central guardian of mitochondrial-immune homeostasis in sepsis,..."

Journal • Hepatology • Infectious Disease • Inflammation • Liver Failure • Metabolic Disorders • Septic Shock • GDF15 • HIF1A • IL6 • PKM • SMAD7 • TNFA • UQCRC1

GDF15 attenuates sepsis-induced acute lung injury by suppressing the HIF-1α/LDHA pathway. (PubMed, Int Immunopharmacol) - "GDF15 emerges as a critical endothelial protector in sepsis by suppressing HIF-1α/LDHA-mediated immunometabolic dysregulation. Its synergistic interplay with glycolytic inhibitors highlights a novel therapeutic strategy to target both inflammatory and metabolic drivers of ALI."

Journal • Acute Lung Injury • Infectious Disease • Inflammation • Metabolic Disorders • Respiratory Diseases • Septic Shock • GDF15 • HIF1A • ICAM1 • IL6 • LDHA • TNFA • VCAM1

Mitochondrial proteome landscape unveils key insights into melanoma severity and treatment strategies. (PubMed, Cancer) - "This study reveals mitochondrial pathways as critical drivers of melanoma progression and resistance, providing a rationale for targeting mitochondrial translation and OXPHOS in advanced melanoma. Combining mitochondrial inhibitors with existing therapies could overcome treatment resistance and improve patient outcomes."

Journal • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • BRAF

Drug sensitivity patterns across FAB subtypes and molecular mutations in AML. (ASCO 2025) - "M1 samples (n=22 patients) demonstrated higher sensitivity to Navitoclax (σsDSS = 15.89), while combinations with mTOR inhibitors like Navitoclax + PF-04691502 (σsDSS = 13.97) and Navitoclax + Vistusertib (σsDSS = 13.72) showed promise...M4 subtypes (n=2 patients) were most sensitive to BAY 87-2243 (σsDSS = 15.98), with dual combinations like BAY 87-2243 + Cerdulatinib (σsDSS = 14.21) and BAY 87-2243 + Pevonedistat (σsDSS = 14.13) maintaining strong responses...In M4 eos (n=9 patients), Pimasertib demonstrated notable effectiveness (σsDSS = 14.43), with dual-agent combination such as Pimasertib + SCH772984 (σsDSS = 14.24) supporting RAS/ERK pathway inhibition. Despite rare M4/M5 subtypes (n=2 patients) showing limited Refametinib sensitivity (σsDSS = 8.75), their minimal sample size precludes definitive conclusions...Likewise, mutation analysis revealed that NPM1-mutated samples showed increased sensitivity to Venetoclax (σsDSS = 13.28) and PF-04691502 (σsDSS =..."

Acute Myelogenous Leukemia • FLT3 • NPM1

Integrating metabolomics and network pharmacology to study the mechanism of Er-Xian Decoction in improving intervertebral disc degeneration. (PubMed, J Ethnopharmacol) - "EXD regulates disc cell metabolism and inflammatory responses by modulating the mTOR and HIF-1 signalling pathways, thereby slowing or reversing IDD."

Journal • Inflammation • Metabolic Disorders • HIF1A • IL1B

Identification of an effective HBV cccDNA inhibitor BAY87-2243 and its potential anti-HBV mechanisms (APASL 2025) - "In summary, we identify BAY87-2243 as a novel and effective inhibitor that reduces cccDNA level, providing a potential new strategy for the complete elimination of chronic HBV infection."

Fibrosis • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Liver Cancer • Oncology • Solid Tumor • LIG1 • LRIG1 • POLD1

HIF-1α Enhances Intestinal Injury and Inflammation in Severe Acute Pancreatitis Through NLRP3 Inflammasome Activation. (PubMed, Dig Dis Sci) - "HIF-1α exacerbates intestinal injury and inflammation in SAP, likely through NLRP3 inflammasome activation. Targeting HIF-1α may offer a potential therapeutic approach for SAP-induced damage and inflammation."

Journal • Inflammation • Pancreatitis • CASP1 • HIF1A • IL1B • NLRP3

Sevoflurane alleviates intestinal ischemia-reperfusion injury in aged mice. (PubMed, Med Gas Res) - "However, preoperative administration of the hypoxia-inducible factor-1α inhibitor BAY87-2243 could counteract the enteroprotective effect of sevoflurane and lower the expression level of heme oxygenase-1, a downstream antioxidant enzyme of hypoxia-inducible factor-1α. Our findings suggest that sevoflurane alleviates intestinal ischemia-reperfusion injury in aged mice by repairing the intestinal mucosal barrier through the activation of hypoxia-inducible factor-1α/heme oxygenase-1, providing a new target for the treatment of intestinal ischemia-reperfusion injury in aged mice."

Journal • Preclinical • Anesthesia • Cardiovascular • Reperfusion Injury • HIF1A • HMOX1

Mitochondria-targeting of oxidative phosphorylation inhibitors to alleviate hypoxia and enhance anticancer treatment efficacy. (PubMed, Clin Cancer Res) - "Here, we review the limitations of the clinically tested OXPHOSi metformin, atovaquone, tamoxifen, BAY 87-2243 and IACS-010759 and the potential of mito-targeted OXPHOSi and their influence on ROS production. Furthermore, the effect of the mitochondria-targeting moiety TPP+ on mitochondria is discussed as this affects mitochondrial bioenergetics."

Journal • Oncology • Solid Tumor

Ciprofol Ameliorates Myocardial Ischemia/Reperfusion Injury by Inhibiting Ferroptosis Through Upregulating HIF-1α. (PubMed, Drug Des Devel Ther) - "Specifically, the protective effects of ciprofol against I/R or H/R injury were abolished by downregulating the expression of HIF-1α using siRNA transfection or the inhibitor BAY87-2243. Ciprofol ameliorated myocardial I/R injury in mice and H/R injury in cardiomyocytes by inhibiting ferroptosis via the upregulation of HIF-1α expression."

Journal • Anesthesia • Cardiovascular • Inflammation • Myocardial Infarction • Myocardial Ischemia • Reperfusion Injury • ACSL4 • GPX4 • HIF1A

Fine-tuning of liposome integrity for differentiated transcytosis and enhanced antitumor efficacy. (PubMed, J Control Release) - "Here, a BAY 87-2243 (a hypoxia-inducible factor-1 inhibitor)-loaded liposomal system (HA-P-LBAY) modified by low molecular weight protamine (LMWP) and crosslinked by hyaluronic acid (HA) was constructed...This highlighted that fine-tuning of structural integrity of nanocarriers played a key role no matter whether the transcytosis of nanocarriers contributed to cellular transport. Collectively, this study provides a promising strategy for antitumor therapies by fine-tuning liposome integrity to achieve active trans-endothelial transport with structural integrity and selective aggregation for prolonged tumor retention."

Journal • Oncology • HIF1A

Hypoxia inducible factor-1α facilitates transmissible gastroenteritis virus replication by inhibiting type I and type III interferon production. (PubMed, Vet Microbiol) - "In vivo experiments in piglets demonstrated that the HIF-1α inhibitor BAY87-2243 significantly reduced HIF-1α expression and inhibited TGEV replication and pathogenesis by activating IFN production. In summary, we unveiled that HIF-1α facilitates TGEV replication by restraining type I and type III IFN production in vitro, ex vivo, and in vivo. The findings from this study suggest that HIF-1α could be a novel antiviral target and candidate drug against TGEV infection."

Journal • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Inflammation • HIF1A

PIEZO1 acts as a cancer suppressor by regulating the ROS/Wnt/β-catenin axis. (PubMed, Thorac Cancer) - "In summary, PIEZO1 acts as a cancer suppressor by regulating the ROS/Wnt/β-catenin axis, providing a new perspective on the role of mechanosensitive channel proteins in cancer."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTNNB1

Targeting HIF-1α alleviates the inflammatory responses and rebuilds the CD4 T cell subsets balance in the experimental autoimmune myasthenia gravis inflammation model via regulating cellular and humoral immunity. (PubMed, Life Sci) - "BAY 87-2243 restored the balance of CD4T cell subsets and reduced the production of the pro-inflammatory cytokines, thus acting as both an immune imbalance regulator and anti-inflammatory. The current study suggests that HIF-1α might be a potential target for the treatment of MG exacerbated with inflammation."

Journal • CNS Disorders • Immunology • Inflammation • Myasthenia Gravis • CD4 • HIF1A • IFNG • IL17A • IL6

Histone acetyltransferase P300 deficiency promotes ferroptosis of vascular smooth muscle cells by activating the HIF-1α/HMOX1 axis. (PubMed, Mol Med) - "Thus, our results revealed that P300 deficiency or inactivation facilitated CD- and IKE-induced VSMC ferroptosis by activating the HIF-1α/HMOX1 axis, which may contribute to the development of diseases related to VSMC ferroptosis."

Epigenetic controller • Journal • Cardiovascular • Developmental Disorders • HIF1A • HMOX1

Using lung-on-a-chip to characterize HIF-1α-dependent inflammatory responses during acute Streptococcus pneumoniae infection (P626) (IMMUNOLOGY 2023) - "Whole human blood with fluorescently-labeled immune cells were perfused in LoC +/- BAY 87-2243 (HIF-1α chemical inhibitor)...IL-17C was identified as the top differentially expressed gene activated by SP and 2D protein analysis showed increased IL-17C levels during HIF-1α knockdown, suggesting that HIF-1α is a negative regulator of IL-17C transcription. These preliminary findings suggest that HIF-1α mediates immune cell recruitment during acute SP infection and support the use of LoC as a pre-clinical human model that can identify key mediators during pneumonia."

Infectious Disease • Inflammation • Pneumococcal Infections • Pneumonia • Respiratory Diseases • HIF1A

NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors. (PubMed, Open Biol) - "We compared the specificity and mode of action of CI inhibitors metformin, BAY 87-2243 and EVP 4593 using cancer cell models devoid of CI...Most of the amino acids involved in such interactions are conserved across species and only rarely found mutated in human. Our data make a case for caution when referring to metformin as a CI-targeting compound, and highlight the need for dosage optimization and careful evaluation of molecular interactions between inhibitors and the holoenzyme."

Journal • Oncology

Metabolic study of hypoxia-inducible factor stabilizers BAY 87-2243, MK-8617, and PT-2385 in equine liver microsomes for doping control. (PubMed, Drug Test Anal) - "This study found 22 metabolites for BAY 87-2243 (19 phase I and three phase II), three metabolites for MK-8617 (all phase I), and five metabolites for PT-2385 (two phase I and three phase II). The major findings of the present study are as follows: (1) all three potential HIF-PHI drug candidates, namely, BAY 87-2243, MK-8617, and PT-2385 are susceptible to oxidation, producing their corresponding hydroxylated metabolites; (2) the ring dissociated metabolites were detected for BAY 87-2243 and PT-2385; (3) in the case of BAY 87-2243 and PT-2385, glucuronic acid conjugated metabolites were detected; and (4) none of the drugs produced sulfonic acid conjugated metabolites."

Journal

Monocarboxylate Transporter 4 in Cancer-Associated Fibroblasts Is a Driver of Aggressiveness in Aerodigestive Tract Cancers. (PubMed, Front Oncol) - "Glycolytic metabolism in fibroblasts was modulated using the HIF-1α inhibitor BAY 87-2243, the antioxidant N-acetyl cysteine, and genetic depletion of MCT4...Moreover, co-injection of ADT carcinoma cells with fibroblasts lacking MCT4 reduces tumor growth and decreases the expression of markers of metabolic compartmentalization in tumors. In conclusion, metabolic compartmentalization with high expression of MCT4 in CAFs drives aggressiveness in ADT cancers."

Journal • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CAFs • HIF1A • MCT1

The protective effects of HIF-1α activation on sepsis induced intestinal mucosal barrier injury in rats model of sepsis. (PubMed, PLoS One) - "The addition of DMOG up-regulated HIF-1α, then decreased the plasma levels of inflammatory mediators, oxidative stress markers, alleviated pathological damage to the intestinal mucosa and decreased intestinal permeability (P < 0.05); while BAY 87-2243 treatment had the opposite effects. Our findings showed that HIF-1α protects the intestinal barrier function of septic rats by inhibiting intestinal inflammation and oxidative damage, our results provide a novel insight for developing sepsis treatment."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Septic Shock • HIF1A

Targeted downregulation of HIF-1α for restraining circulating tumor microemboli mediated metastasis. (PubMed, J Control Release) - "While knock-out of HIF-1α or therapeutically downregulating of HIF-1α via HIF-1α inhibitor (BAY87-2243)-loaded neutrophil cyto-pharmaceuticals (PNEs) could efficiently restrain CTM mediated lung metastasis...Thus, our work here illustrates that hypoxia was an essential factor in promoting CTM colonization in lung. More importantly, we provide a promising strategy by targeted downregulation of HIF-1α in CTM via neutrophil cyto-pharmaceuticals for treatment of CTM mediated metastasis."

Journal • Oncology • CTCs • HIF1A • PD-L1