Arecoline HBr
ACAT1 inhibitor / Tyrosine407 phosphorylation activates mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) by stabilizing its tetramer. This is believed to be the mechanisms by which ACAT1 is “hijacked” and contributes to the Warburg effect in cancer. Arecoline is a covalent inhibitor of ACAT1 which binds to and disrupts only ACAT1 tetramers (IC50=11.1 μM). ACAT2 and DLAT are not inhibited. Treatment of xenograft nude mice with Arecoline resulted in a dose-dependent reduction in tumor mass.1 Agonist at muscarinic acetylcholine receptors M1 – M5 (EC50 in the range of 7-410 nM).2 May be effective in dementia.3
Biochemicals & reagents
300-08-3
1) Fan et al. (2016), Tetrameric Acetyl-CoA Acetyltransferase 1 is Important for Tumor Growth; Mol. Cell, 64 859 2) Heinrich et al. (2009), Pharmacological comparison of muscarinic ligands: historical versus more recent muscarinic M1-preferring receptor agonists; Eur. J. Pharmacol., 605 53 3) Christie et al. (1981), Physostigmine and arecoline: effects of intravenous infusions in Alzheimer presenile dementia; Br. J. Psychiatry, 138 46
RT
TARGET: Acetyltransferase; GPCR -- PATHWAY: Fatty acid metabolism; ACh (Acetylcholine) signaling; Warburg effect; Chromatin -- RESEARCH AREA: Neuroscience -- DISEASE AREA: Cancer; NeurodegenerationInfectious disease