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Substrates and Inhibitors of Human Multidrug Resistance Associated Proteins and the Implications in Drug Development

Zhou, Shu-Feng, Wang, Lin-Lin, Di, Yuan, Xue, Charlie, Duan, Wei, Li, Chun, Li, Yong·2008·Current Medicinal Chemistry
DOI 10.2174/092986708785132870
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Abstract

Human contains 49 ATP-binding cassette (ABC) transporter genes and the multidrug resistance associated proteins (MRP1/ABCC1, MRP2/ABCC2, MRP3/ABCC3, MRP4/ABCC4, MRP5/ABCC5, MRP6/ABCC6, MRP7/ABCC10, MRP8/ABCC11 and MRP9/ABCC12) belong to the ABCC family which contains 13 members. ABCC7 is cystic fibrosis transmembrane conductance regulator; ABCC8 and ABCC9 are the sulfonylurea receptors which constitute the ATP-sensing subunits of a complex potassium channel. MRP10/ABCC13 is clearly a pseudo-gene which encodes a truncated protein that is highly expressed in fetal human liver with the highest similarity to MRP2/ABCC2 but without transporting activity. These transporters are localized to the apical and/or basolateral membrane of the hepatocytes, enterocytes, renal proximal tubule cells and endothelial cells of the blood-brain barrier. MRP/ABCC members transport a structurally diverse array of important endogenous substances and xenobiotics and their metabolites (in particular conjugates) with different substrate specificity and transport kinetics. The human MRP/ABCC transporters except MRP9/ABCC12 are all able to transport organic anions, such as drugs conjugated to glutathione, sulphate or glucuronate. In addition, selected MRP/ABCC members may transport a variety of endogenous compounds, such as leukotriene C(4) (LTC(4) by MRP1/ABCC1), bilirubin glucuronides (MRP2/ABCC2, and MRP3/ABCC3), prostaglandins E1 and E2 (MRP4/ABCC4), cGMP (MRP4/ABCC4, MRP5/ABCC5, and MRP8/ABCC11), and…

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Metadata

Authors
Zhou, S.-F., Wang, L.-L., Di, Y., Xue, C., Duan, W., Li, C., & Li, Y.
Venue
Current Medicinal Chemistry
Publisher
Bentham Science Publishers Ltd.
Published
2008-08-01
Volume
15
Issue
20
Pages
1981-2039
ISSN
0929-8673
DOI
10.2174/092986708785132870
Cited by
318
References
0
Language
en

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