gw-4064 and Cholestasis--Intrahepatic

gw-4064 has been researched along with Cholestasis--Intrahepatic* in 1 studies

Other Studies

1 other study(ies) available for gw-4064 and Cholestasis--Intrahepatic

Article	Year
Discovery and structural development of small molecules that enhance transport activity of bile salt export pump mutant associated with progressive familial intrahepatic cholestasis type 2. Bioorganic & medicinal chemistry, 2012, May-01, Volume: 20, Issue:9 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. Here, we show that bile acids possibly act as pharmacological chaperones, promoting the proper folding and trafficking of E297G BSEP. We also describe the discovery and structural development of non-steroidal compounds with potent pharmacological chaperone activity for E297G BSEP. Topics: Amino Acid Substitution; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Bile Acids and Salts; Biological Transport; Cell Line; Cholestasis, Intrahepatic; Dogs; Drug Evaluation, Preclinical; Endoplasmic Reticulum; Gene Expression; Isoxazoles; Mutation; Phenylbutyrates; Structure-Activity Relationship	2012

Article

Year

Discovery and structural development of small molecules that enhance transport activity of bile salt export pump mutant associated with progressive familial intrahepatic cholestasis type 2.

Bioorganic & medicinal chemistry, 2012, May-01, Volume: 20, Issue:9

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. Here, we show that bile acids possibly act as pharmacological chaperones, promoting the proper folding and trafficking of E297G BSEP. We also describe the discovery and structural development of non-steroidal compounds with potent pharmacological chaperone activity for E297G BSEP.

Topics: Amino Acid Substitution; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Bile Acids and Salts; Biological Transport; Cell Line; Cholestasis, Intrahepatic; Dogs; Drug Evaluation, Preclinical; Endoplasmic Reticulum; Gene Expression; Isoxazoles; Mutation; Phenylbutyrates; Structure-Activity Relationship

2012