BAY 872243 / Bayer - LARVOL DELTA

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

The HIF-1α pathway plays a critical role in salivary gland development in ex vivo organ cultures. (PubMed, FEBS Open Bio) - "We further showed that BAY 87-2243-mediated inhibition of HIF-1α suppressed salivary gland development...Additionally, using the inhibitor U0126, we verified that the ERK1/2 pathway is upstream of HIF-1α. Overall, we found that the HIF-1α signaling pathway plays a critical role in salivary gland development in ex vivo SMG organ cultures."

Journal • Preclinical • HIF1A

EVT-701 is a novel selective and safe mitochondrial complex 1 inhibitor with potent anti-tumor activity in models of solid cancers. (PubMed, Pharmacol Res Perspect) - "The anticancer effect exerted by the pleiotropic drug metformin and the associated reduction in hypoxia-inducible factor 1α (HIF-1α) levels putatively mediated by MC1 inhibition led to the development of HIF-1α inhibitors, such as BAY87-2243, with a more specific MC1 targeting. LKB1 deficiency in lung cancer was identified as a potential indicator of accrued sensitivity to EVT-701, allowing stratification and selection of patients in clinical trials. Altogether these results support further evaluation of EVT-701 alone or in combination in preclinical models and eventually in patients."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lung Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • HIF1A • STK11

Activation of macrophage TBK1-HIF-1α-mediated IL-17/IL-10 signaling by hyperglycemia aggravates the complexity of coronary atherosclerosis: An in vivo and in vitro study. (PubMed, FASEB J) - "THP-1 cell studies showed that BAY87-2243 (a HIF-1α inhibitor) reversed the increase in IL-17 and decrease in IL-10 expression induced by hyperglycemia. We conclude that hyperglycemia might aggravate the complexity of coronary atherosclerosis through activation of TBK1-HIF-1α-mediated IL-17/IL-10 signaling. Thus, TBK1 may be a novel drug therapy target for CHD complicated with DM."

Journal • Preclinical • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Heart Failure • Metabolic Disorders • Myocardial Infarction • HIF1A • IL10 • IL17A

Baicalin promotes extracellular matrix synthesis in chondrocytes via the activation of hypoxia-inducible factor-1α. (PubMed, Exp Ther Med) - "In total, 44 µM BA and 10 µM hypoxia-inducible-factor-1α (HIF-1α) inhibitor BAY-87-2243 were screened by the [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] method...The findings of the present study suggest that BA may promote ECM synthesis and marker gene expression in chondrocytes by activating HIF-1α. Therefore, BA may represent a novel clinical drug for OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • HIF1A • MMP13 • MMP9 • SOX9

[VIRTUAL] Hypoxia-Inducible Factor 1 Alpha Regulates FGF-23 Production and Bone Metabolism in CKD (KIDNEY WEEK 2020) - "In parallel, we also treated 6 week-old WT and Col4a3KO mice with a HIF inhibitor (BAY 87-2243) for 4 weeks... Our data suggest that osseous HIF1α stimulates FGF23 production in CKD and is a negative regulator of osteoblast differentiation and function. Thus, inhibition of HIF1α in bone might represent a novel therapeutic strategy to improve bone and mineral outcomes in CKD. Funding: NIDDK Support"

Cardiovascular • Chronic Kidney Disease • Nephrology • Orthopedics • Renal Disease • Collagen Type IV • FGF • FGF23 • HIF1A

[VIRTUAL] Exosomes from Intermittent Hypoxia Treated Lung Adenocarcinoma Cell Line Up-regulate Programmed Death Ligand 1 Expression through HIF-1a Pathway in Macrophages (ERS 2020) - "Specific HIF-1α inhibitor BAY87-2243 inhibited the upregulation of PD-L1 expression in the Exo-IH Group. CONCLUSION Exosomes from intermittent hypoxia treated lung adenocarcinoma cell line up-regulate PD-L1 expression through HIF-1α pathway in macrophages."

IO Biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Obstructive Sleep Apnea • Oncology • Sleep Disorder • Solid Tumor • HIF1A • PD-1 • PD-L1

Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate. (PubMed, Cell Rep) - "Inhibition of oxidative phosphorylation (OXPHOS) by 1-cyclopropyl-4-(4-[(5-methyl-3-(3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl]pyridin-2-yl)piperazine (BAY87-2243, abbreviated as B87), a complex I inhibitor, fails to kill human cancer cells in vitro...Simultaneous inhibition of OXPHOS and glycolysis provoked a bioenergetic catastrophe culminating in the activation of a cell death program that involved disruption of the mitochondrial network and activation of PARP1, AIFM1, and APEX1. These results unveil a metabolic liability of human cancer cells that may be harnessed for the development of therapeutic regimens."

Journal • Oncology

Hypoxia-dependent HIF-1 activation impacts on tissue remodeling in Graves' ophthalmopathy - implications for smoking. (PubMed) - "Hypoxia impacts on tissue remodeling in GO by stimulating angiogenesis and adipogenesis through activation of HIF-1-dependent pathways in OFs. Our results offer a molecular mechanism for the detrimental influence of smoking on GO and an explanation as to why decompression can improve the outcome of patients. Drug-targeted inhibition of HIF-1/VEGF may provide a therapeutic option to control tissue expansion in GO."

Journal • Biosimilar • Immunology • Ophthalmology