AAA-10 is an orally active gut bacterial bile salt hydrolases (BSH) inhibitor, with IC50s of 10 nM, 80 nM against B. theta rBSH and B. longum rBSH respectively[1].
AAA-10 (100 μM; 24 h) inhibits BSH activity in bacterial cultures, with IC50s of 74 nM, 901 nM for Gram-negative and Gram-positive bacteria, respectively[1]. AAA-10 (20 μM; 2 h) significantly inhibits deconjugation of glycochenodeoxycholic acid-d4 or taurocholic acid-d4 substrates of human feces[1].
AAA-10 (30 mg/kg; orally gavage daily for 5 days) decreases the abundances of deoxycholic acid (DCA) and lithocholic acid (LCA) in mice feces starting in day 2-5[1].AAA-10 (30 mg/kg) displays high colonic exposure and low gut permeability[1].
[1]. Adhikari AA, et al. A Gut-Restricted Lithocholic Acid Analog as an Inhibitor of Gut Bacterial Bile Salt Hydrolases. ACS Chem Biol. 2021;16(8):1401-1412.