ETC-1002 works as an AMPK activator. ETC-1002 at 100μM increased levels of AMPK phosphorylation in primary human MDMs exposure to LPS, and decreased production of proinflammatory cytokines and chemokines. In dyslipidemic subjects, ETC-1002 not only reduces plasma LDL cholesterol but also significantly attenuates levels of hsCRP, a clinical biomarker of inflammation. Silencing of LKB1 by siRNA could significantly abrogate AMPK phosphorylation and inhibitory effects of ETC-1002 on soluble mediators of inflammation. ETC-1002 suppressed thioglycollate-induced homing of leukocytes into mouse peritoneal cavity in vivo. Also, it restored adipose AMPK activity, reduced JNK phosphorylation, and diminished expression of macrophage-specific marker 4F/80 in a mouse model of diet-induced obesity. ETC-1002 is an investigational drug currently in Phase 2 development for treatment of dyslipidemia and other cardiometabolic risk factors[2].
Bempedoic acid 细胞实验
Cell Line
Concentration
Treated Time
Description
References
AML12 hepatocytes
30 μM
16 hours
Fostered lipid accumulation and reduced mitochondrial metabolic activity
Aging Cell. 2024 Sep;23(9):e14205.
RAW-BlueTM cells
25 µM
24 hours
Assessed NF-κB/AP-1 activity, showing minimal impact of bempedoic acid on macrophage inflammatory responses.
Int J Mol Sci. 2021 Nov 19;22(22):12480.
Primary human hepatocytes
100 μM
18-20 hours
To evaluate the effect of ETC-1002 on cholesterol synthesis, results showed that ETC-1002 reduced cholesterol and fatty acid synthesis.
Nat Commun. 2016 Nov 28;7:13457.
McArdle cells
30 μM
48 hours
To study ETC-1002-CoA synthetase activity, results showed that ACSVL1 siRNA treatment reduced ETC-1002-CoA formation.
Nat Commun. 2016 Nov 28;7:13457.
Pkd1-null kidney cells (IMCD-derived)
100 µM
3 days
Inhibited cystic growth, reduced cyst area
Front Mol Biosci. 2022 Nov 25;9:1001941.
Pkd1-null kidney cells (PT-derived)
100 µM
3 days
Inhibited cystic growth, reduced cyst area
Front Mol Biosci. 2022 Nov 25;9:1001941.
Bone marrow-derived macrophages (BMMs)
25 µM
24 hours
Measured TNF and IL1β secretion and gene expression, finding no significant effect of bempedoic acid on macrophage inflammatory responses.
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