SLC26A3-IN-2 is an orally active inhibitor of anion exchanger protein SLC26A3 (IC50=360 nM). SLC26A3 belongs to solute carrier (SLC) proteins, and the SLC26 family. SLC26 family has broad anion specificity for chloride, bicarbonate, sulfate and oxalate. SLC26A3 down-regulates in adenoma, DRA, involves in in intestinal absorption of chloride and oxalate. The loss of SLC26A3 function mutations is associated with chloride-losing diarrhea.
SLC26A3-IN-2 (compound 3a) (10 μM; 10 min) produces 92% inhibition rate against SLC26A3[1].
SLC26A3-IN-2 (10 mg/kg; po) significantly increases stool weight and number of pellets in a Loperamide -induced model of constipation in mice, demonstrating its efficacy in increasing stool hydration in mice[1].
References:
[1]. Cil O, et al. Small molecule inhibitors of intestinal epithelial anion exchanger SLC26A3 (DRA) with a luminal, extracellular site of action. Eur J Med Chem. 2023 Mar 5;249:115149.