COMMENT: Research about the ABC transporters has been skyrocketing in the last 3 years. These transporters also are involved in drug transport in many organs of the body including both reabsorption and tubular secretion in the kidney. Best known of this group, ABCB1 or also known as p-glycoprotein has occupied the forefront of research. Like ABCB1, there are other 2 other important ABC transporters that are involved in multidrug resistance (MDR), ABCC1 and ABCG2. This article reviews the methodology that is used to categorize the substrates and particularly important, the inhibitors of the ABC transporters involved in MDR-ABCB1, ABCC1 and ABCG2. The quest to find inhibitors of these transporters will have enormous clinical value since they can inhibit MDR and thus allow oncologic drugs to continue to be effective.
Curr Drug Deliv. 2007 Oct;4(4):324-33.
ABC drugtransporters as molecular targets for the prevention of multidrug resistance and drug-drug interactions.
Calcagno AM, Kim IW, Wu CP, Shukla S, Ambudkar SV.Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH/DHHS, Bethesda, MD 20892, USA.firstname.lastname@example.org
ABC transporters play an important role in mediating the cytoplasmic concentration of endogenous and xenobiotic substances. They therefore influence the pharmacokinetic profile of a variety of drugs. By virtue of their localization to plasma membranes in the intestine, liver, blood-brain and other vital biological barriers, a majority of ABC drug transporters cause drug-drug interactions, decreased drug efficacy and multidrug resistance for chemotherapeutic agents. Thus, elucidating which drug entities are substrates for ABC drug transporters is a crucial step in the drug development and treatment process. Here, we review the current status of methodology used to categorize drug compounds as substrates or modulators for the major ABC drug transporters including ABCB1, ABCC1 and ABCG2. PMID: 17979652