An orally bioavailable trisubstituted thiourea compound that acts as a potent, uncompetitive and reversible inhibitor of bacterial b-glucuronidase activity (IC50 = 283nM; kcat/Km=0.0987s-1uM-1; Ki4nM in vitro assays against E. coli b-glucuronidase; EC50.7nM in b-glucuronidase expressing HB101 cells) with excellent selectivity over mammalian b-glucuronidases. Shown to directly target the 17-residue (360-376) loop structure that protects the active site of E. coli b-glucuronidase and alter its conformation. Displays negligible cytotoxicity toward both bacterial and mammalian epithelial cells (>100uM for HCT116, Caco-2 and CMT93 colon cancer cells) and offers protection against CPT-11 (50mg/kg, i.p., s.i.d. for 9 days)-induced toxicity in mice (10ug, p.o., b.i.d).
Formula:C₂₃H₂₇N₃O₃S
Molecular Weight:425.5
Solubility:DMSO (50mg/ml)
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with s dH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. Reconstituted product is stable for 6 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
