title: Involvement of Drug Transporters in Organ Toxicity: The Fundamental Basis of Drug Discovery and Development.
abstract: Membrane transporters play a pivotal role in many organs to maintain their normal physiological functions and contribute significantly to drug absorption, distribution, and elimination. Knowledge gained from gene modified animal models or human genetic disorders has demonstrated that interruption of the transporter activity can lead to debilitating diseases or organ toxicities. Herein we describe transporter associated diseases and organ toxicities resulting from transporter gene deficiency or functional inhibition in the liver, kidney, gastrointestinal tract (GIT), and central nervous system (CNS). While proposing additional transporters as targets for drug-induced organ toxicity, strategies and future perspectives are discussed for transporter risk assessment in drug discovery and development.
authors.affiliation: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company , 3551 Lawrenceville Road, Princeton, New Jersey 08540, United States.
authors.forename: Yaofeng
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc. , 610 Main Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Kattan
authors.affiliation: Drug Metabolism and Biopharmaceutics, Incyte Corporation , 1801 Augustine Cutoff, Wilmington, Delaware 19803, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Drug Metabolism, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Ray
authors.affiliation: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company , 3551 Lawrenceville Road, Princeton, New Jersey 08540, United States.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Lai
mesh_terms: D000818:Animals; D001692:Biological Transport; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations