Arecoline Hydrobromide is a betel nut alkaloid. Its has shown to activate critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1) and glucose transporter 2 (GLUT-2). Tyrosine 407 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 mM). ACAT2 and DLAT are not inhibited. Treatment of xenograft nude mice with Arecoline resulted in a dose-dependent reduction in tumor mass. Agonist at muscarinic acetylcholine receptors M1 – M5 (EC50 in the range of 7-410 nM). May be effective in dementia, in healthy volunteers it has shown to improve learning abilities.
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