Discovery and structural development of small molecules that enhance transport activity of bile salt export pump mutant associated with progressive familial …

…, H Hayashi, Y Sugiyama, Y Hashimoto

Index: Misawa, Takashi; Hayashi, Hisamitsu; Sugiyama, Yuichi; Hashimoto, Yuichi Bioorganic and Medicinal Chemistry, 2012 , vol. 20, # 9 p. 2940 - 2949

Full Text: HTML

Citation Number: 12

Abstract

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by hereditary mutations of bile salt export pump (BSEP), such as E297G BSEP, which is a folding- defective mutant that is unable to traffic beyond the endoplasmic reticulum (ER). 4- Phenylbutyric acid (4-PBA) enhances the cell surface expression and transport capacity of E297G BSEP, but has a relatively high dose (1mM or more) is required to show the effect. ...