title: Apical sodium dependent bile acid transporter (ASBT, SLC10A2): a potential prodrug target.
abstract: A major hurdle impeding the successful clinical development of drug candidates can be poor intestinal permeability. Low intestinal permeability may be enhanced by a prodrug approach targeting membrane transporters in the small intestine. Transporter specificity, affinity, and capacity are three factors in targeted prodrug design. The human apical sodium dependent bile acid transporter (SLC10A2) belongs to the solute carrier family (SLC) of transporters and is an important carrier protein expressed in the small intestine. In spite of its appearing to be an excellent target for prodrug design, few studies have targeted human apical sodium dependent bile acid transporter (hASBT) to improve oral bioavailability. This review discusses bile acids including their chemistry and their absorptive disposition. Additionally, hASBT-mediated prodrug targeting is discussed, including QSAR, in vitro models for hASBT assay, and the current progress in utilizing hASBT as a drug delivery target.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: James E
authors.initials: JE
authors.lastname: Polli
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism*; D001682:Biological Availability; D001692:Biological Transport; D002460:Cell Line; D016503:Drug Delivery Systems; D004764:Enterohepatic Circulation; D006801:Humans; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D027981:Symporters / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; D029363:Organic Anion Transporters, Sodium-Dependent; D011355:Prodrugs; D027981:Symporters; C071908:sodium-bile acid cotransporter