BAY-3827 is a potent and selective AMP-activated protein kinase (AMPK) inhibitor with IC50 values of 1.4nM at low ATP concentration (10µM) and 15nM at high ATP concentration (2mM)[1]. AMPK is a global sensor of cellular energy levels and a key regulator of nutrient metabolism[2]. BAY-3827 inhibits the phosphorylation of acetyl-CoA carboxylase (ACC)[3].
In vitro, treatment of human prostate cancer cell lines (LNCaP, VCaP cells) with BAY-3827 (1nM) for 24h or 48h downregulated the expression of multiple genes involved in lipid metabolism, such as LIPE, PRKAR2B, AKT3, and CPT1 family members[4]. Pretreatment of cardiac fibroblasts (HCFs) with BAY-3827 (500nM) for 1h effectively eliminated the phosphorylation of intracellular acetyl-CoA carboxylase (ACC) induced by SGLT2i[5]. Treatment of corneal epithelial cells infected with Pseudomonas aeruginosa (PA) with BAY-3827 (10µM) significantly reduced the levels of inflammatory markers IL-6 and IL-8 in the cells[6].
In vivo, stereotactic injection of BAY-3827 (5µL, 100µM) into neurotrophic tyrosine kinase receptor 1 (NTRK1) knockdown mice exacerbated the impairment of working memory and reference memory, and exacerbated depressive-like behavior[7].
References:
[1] Lemos C, Schulze V K, Baumgart S J, et al. The potent AMPK inhibitor BAY-3827 shows strong efficacy in androgen-dependent prostate cancer models[J]. Cellular Oncology, 2021, 44(3): 581-594.
[2] He L, Zhou X, Huang N, et al. AMPK regulation of glucose, lipid and protein metabolism: mechanisms and nutritional significance[J]. Current Protein and Peptide Science, 2017, 18(6): 562-570.
[3] Strang J E, Astridge D D, Nguyen V T, et al. Small molecule modulators of AMP-activated protein kinase (AMPK) activity and their potential in cancer therapy[J]. Journal of Medicinal Chemistry, 2025, 68(3): 2238-2254.
[4] Lemos C, Schulze V K, Baumgart S J, et al. The Potent and Selective AMPK Inhibitor BAY-3827 Shows Strong Efficacy in Androgen-Dependent Prostate Cancer Models[J]. 2020.
[5] Baufays C, Cumps J, Dufeys C, et al. Comparison of the Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiac Fibroblast Properties[J]. International Journal of Molecular Sciences, 2025, 26(20): 10098.
[6] Cao D W, Ramachandran R A, Robertson D M. AMPK modulates mitochondrial homeostasis during Pseudomonas aeruginosa infection in corneal epithelial cells[J]. Investigative Ophthalmology & Visual Science, 2024, 65(7): 1971-1971.
[7] Yang K, Wu J, Li S, et al. NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway[J]. Cell Death Discovery, 2023, 9(1): 404.
BAY-3827是一种强效且选择性的AMP活化蛋白激酶（AMPK）抑制剂，在低浓度ATP（10µM）下IC50值为1.4nM，在高浓度ATP（2mM）下为15nM[1]。AMPK是细胞能量水平的总传感器，也是营养物质代谢的关键调节器[2]。BAY-3827能够抑制乙酰辅酶A羧化酶（ACC）的磷酸化[3]。
在体外，BAY-3827（1nM）处理人类前列腺癌细胞系（LNCaP、VCaP细胞）24h或48h，下调了多个参与脂质代谢的基因的表达，例如LIPE、PRKAR2B、AKT3和CPT1家族成员[4]。BAY-3827（500nM）预处理心肌成纤维细胞（HCFs）1h，有效消除了SGLT2i诱导的细胞内乙酰辅酶A羧化酶（ACC）的磷酸化[5]。BAY-3827（10µM）处理感染铜绿假单胞菌（PA）的角膜上皮细胞，显著降低了细胞中炎症标志物IL-6和IL-8的水平[6]。
在体内，BAY-3827（5µL, 100µM）通过脑立体定向注射处理神经营养酪氨酸激酶受体1（NTRK1）敲低小鼠，加剧了小鼠的工作记忆和参考记忆损伤，加剧了抑郁样行为[7]。