BAY-3827 / Bayer - LARVOL DELTA

Comparison of the Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiac Fibroblast Properties. (PubMed, Int J Mol Sci) - "Recent clinical trials have shown significant cardioprotective effects of antidiabetic sodium-glucose cotransporter 2 inhibitors (SGLT2i), including canagliflozin, empagliflozin, and dapagliflozin...In contrast, the effect of canagliflozin on migration was partially dependent on AMPK, as demonstrated using the AMPK inhibitor BAY-3827. These findings reveal distinct cellular effects of individual SGLT2i on cardiac fibroblasts, suggesting heterogeneous potential to modulate extracellular matrix remodeling. Among them, canagliflozin may be more potent in preventing myocardial fibrosis in the context of heart failure."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Metabolic Disorders • AMPK

Mechanism and cellular actions of the potent AMPK inhibitor BAY-3827. (PubMed, Sci Adv) - "Transcriptome analysis revealed that BAY-3827 down-regulated ~30% of MK-8722-stimulated AMPK-dependent genes. We establish the molecular and cellular basis of BAY-3827's selectivity and utility for delineating AMPK functions while highlighting its limitations."

Journal • AMPK

Metformin Enhances the Chemosensitivity of Gastric Cancer to Cisplatin by Downregulating Nrf2 Level. (PubMed, Anal Cell Pathol (Amst)) - "BAY-3827 (AMPK inhibitor) or p-nitro-Pifithrin-α (p53 inhibitor) treatments also reversed the effects of metformin increased the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. These results suggest that metformin significantly increases chemosensitivity of gastric cancer to cisplatin by inhibiting Nrf2 expression and metabolic reprogramming and activating oxidative stress and the pathway of p53 and AMPK."

Journal • Gastric Cancer • Oncology • Solid Tumor • NFE2L2

AMP-activated protein kinase mediates adaptation of glioblastoma cells to conditions of the tumor microenvironment. (PubMed, J Exp Clin Cancer Res) - "AMPK activity was modulated genetically by CRISPR/Cas9-based double knockout (DKO) of the catalytic α1 and α2 subunits in human GB cells and effects were confirmed by pharmacological AMPK inhibition using BAY3827 and an inactive control compound in primary GB cell cultures...Moreover, we identified mitochondria as central downstream effectors of AMPK signaling. The development of AMPK inhibitors could open opportunities for the treatment of hypoxic tumors."

Biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Netrin-1 binding to UNC5b improves post-stroke neuronal ferroptosis via AMPK-BACH1 pathway. (PubMed, Eur J Pharmacol) - "AMPK inhibitor BAY3827 and BACH1 activator Leptomycin B (LMB) were administrated...Co-immunoprecipitation verified that AMPK could physically bind to BACH1. Our results demonstrate UNC5b-evoked neuronal ferroptosis post stroke, and favor that Ntn1 improves post-stroke ferroptosis by its interaction with UNC5b via the AMPK-BACH1 pathway."

Journal • Cardiovascular • Hematological Disorders • Ischemic stroke • Thrombosis • ACSL4 • AIFM2 • BACH1 • BRIP1 • GPX4 • NTN1

A Skeletal Muscle-Mediated Anticontractile Response on Vascular Tone: Unraveling the Lactate-AMPK-NOS1 Pathway in Femoral Arteries. (PubMed, Function (Oxf)) - "Phosphorylation of NOS1 was reduced in the presence of Bay-3827, a selective AMPK inhibitor...Mechanistically, the anti-contractile effect involves muscle fiber type and/or its anatomical location but not the type of artery or its related vascular endothelium. Finally, the femoral artery anti-contractile effect is mediated by the lactate-AMPK-phospho-NOS1Ser1417-NO signaling axis."

Journal • NOS1

AMPK inhibition sensitizes acute leukemia cells to BH3 mimetic-induced cell death. (PubMed, Cell Death Differ) - "BH3 mimetics, including the BCL2/BCLXL/BCLw inhibitor navitoclax and MCL1 inhibitors S64315 and tapotoclax, have undergone clinical testing for a variety of neoplasms...Building on the observation that BH3 mimetic monotherapy induces AMP kinase (AMPK) activation in multiple acute leukemia cell lines, we report that the AMPK inhibitors (AMPKis) dorsomorphin and BAY-3827 sensitize these cells to navitoclax or MCL1 inhibitors...Conversely, dorsomorphin synergizes with navitoclax or the MCL1 inhibitor S63845 to induce cell death in primary acute leukemia samples ex vivo and increases the antitumor effects of navitoclax or S63845 in several xenograft models in vivo with little or no increase in toxicity in normal tissues. These results suggest that AMPK inhibition can sensitize acute leukemia to multiple BH3 mimetics, potentially allowing administration of lower doses while inducing similar antineoplastic effects."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia • AMPK • BCL2 • BCL2L1 • BCL2L2

BAY-3827 and SBI-0206965: Potent AMPK Inhibitors That Paradoxically Increase Thr172 Phosphorylation. (PubMed, Int J Mol Sci) - "Surprisingly, the two inhibitors appear to promote Thr172 phosphorylation by different mechanisms: BAY-3827 primarily protects against Thr172 dephosphorylation, while SBI-0206965 also promotes phosphorylation by LKB1 at low concentrations, while increasing cellular AMP:ATP ratios at higher concentrations. Due to its greater potency and fewer off-target effects, BAY-3827 is now the inhibitor of choice for cell studies, although its low bioavailability may limit its use in vivo."

Journal • Diabetes • Hepatology • Lung Adenocarcinoma • Lung Cancer • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • AMPK • STK11

NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway. (PubMed, Cell Death Discov) - "A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage...Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • NTRK • NTRK1

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AMPK

The potent AMPK inhibitor BAY-3827 shows strong efficacy in androgen-dependent prostate cancer models. (PubMed, Cell Oncol (Dordr)) - "The availability of the potent inhibitor BAY-3827 will contribute to a better understanding of the role of AMPK signaling in cancer, especially in prostate cancer."

Clinical • Journal • Preclinical • Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor • AMPK • AR • FASN