Topological Polar Surface Area Defines Substrate Transport by Multidrug Resistance Associated Protein 1 (MRP1/ABCC1)

被引：93

作者：

Fernandes, Janaina ^{[1
]}

Gattass, Cerli R. ^{[1
]}

机构：

[1] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ctr Ciencias Saude, Lab Imunol Celular, BR-21949900 Rio De Janeiro, Brazil

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 04期

关键词：

GLUTATHIONE-S-TRANSFERASE; MEDIATED VINCRISTINE RESISTANCE; ATP-DEPENDENT EFFLUX; LEUKOTRIENE C-4; P-GLYCOPROTEIN; MRP1; CONJUGATE; INHIBITION; DRUGS; DETOXIFICATION;

D O I：

10.1021/jm801389m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a very promiscuous transporter. Herein we used topological polar surface area (TPSA), a descriptor defined as the sum of surfaces of polar atoms in a molecule, to analyze drug transport by MRP1. We suggested that compounds with high TPSA are transported while those with low TPSA are not. The conjugation to GSH increases TPSA values favoring transport. A strong correlation between TPSA and transport properties (K-m) was also found.

引用

页码：1214 / 1218

页数：5

共 49 条

[1] Multidrug Resistance-Associated Protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine Sulfoximine
Akan, Ilhan
Akan, Selma
Akca, Hakan
Savas, Burhan
Ozben, Tomris
[J]. CANCER CELL INTERNATIONAL, 2005, 5 (1)
[2] Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions
Bakos, É
Evers, R
Sinkó, E
Váradi, A
Borst, P
Sarkadi, B
[J]. MOLECULAR PHARMACOLOGY, 2000, 57 (04) : 760 - 768
[3] On the putative co-transport of drugs by multidrug resistance proteins
Borst, P
Zelcer, N
van de Wetering, K
Poolman, B
[J]. FEBS LETTERS, 2006, 580 (04) : 1085 - 1093
[4] Oleanolic acid inhibits the activity of the multidrug resistance protein ABCC1 (MRP1) but not of the ABCB1 (P-glycoprotein): Possible use in cancer chemotherapy
Braga, F.
Ayres-Saraiva, D.
Gattass, C. R.
Capella, M. A. M.
[J]. CANCER LETTERS, 2007, 248 (01) : 147 - 152
[5] Chen ZS, 1999, MOL PHARMACOL, V55, P921
[6] Cnubben NHP, 1998, CANCER RES, V58, P4616
[7] Transport of glutathione and glutathione conjugates by MRP1
Cole, Susan P. C.
Deeley, Roger G.
[J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2006, 27 (08) : 438 - 446
[8] Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins
Deeley, Roger G.
Westlake, Christopher
Cole, Susan P. C.
[J]. PHYSIOLOGICAL REVIEWS, 2006, 86 (03) : 849 - 899
[9] DELOU JMA, MOL MED REP IN PRESS
[10] Glutathione S-transferase M1 and multidrug resistance protein 1 Act in synergy to protect melanoma cells from vincristine effects
Depeille, P
Cuq, P
Mary, S
Passagne, I
Evrard, A
Cupissol, D
Vian, L
[J]. MOLECULAR PHARMACOLOGY, 2004, 65 (04) : 897 - 905

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