SLC transporters as therapeutic targets: emerging opportunities

被引：598

作者：

Lin, Lawrence ^{[1
,2
]}

Yee, Sook Wah ^{[1
,2
]}

Kim, Richard B. ^{[3
]}

Giacomini, Kathleen M. ^{[1
,2
,4
]}

机构：

[1] Univ Calif San Francisco, Sch Pharm, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Sch Med, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA

[3] Univ Western Ontario, London Hlth Sci Ctr, Dept Med, Div Clin Pharmacol, London, ON N6A 5A5, Canada

[4] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2015年 / 14卷 / 08期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

GENOME-WIDE ASSOCIATION; AMINO-ACID TRANSPORTER; VESICULAR MONOAMINE TRANSPORTER-2; EXHIBITS ANTIDIABETIC EFFICACY; POSITRON-EMISSION-TOMOGRAPHY; GLUCOSE COTRANSPORTER SGLT1; DRUG-DRUG INTERACTIONS; CANCER-CELL-GROWTH; GLUTAMATE TRANSPORTER; BILE-ACID;

D O I：

10.1038/nrd4626

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Solute carrier (SLC) transporters a family of more than 300 membrane-bound proteins that facilitate the transport of a wide array of substrates across biological membranes have important roles in physiological processes ranging from the cellular uptake of nutrients to the absorption of drugs and other xenobiotics. Several classes of marketed drugs target well-known SLC transporters, such as neurotransmitter transporters, and human genetic studies have provided powerful insight into the roles of more-recently characterized SLC transporters in both rare and common diseases, indicating a wealth of new therapeutic opportunities. This Review summarizes knowledge on the roles of SLC transporters in human disease, describes strategies to target such transporters, and highlights current and investigational drugs that modulate SLC transporters, as well as promising drug targets.

引用

页码：543 / 560

页数：18

共 214 条

[91] A Genome-Wide Scan of Ashkenazi Jewish Crohn's Disease Suggests Novel Susceptibility Loci [J].

Kenny, Eimear E. ;

Pe'er, Itsik ;

Karban, Amir ;

Ozelius, Laurie ;

Mitchell, Adele A. ;

Ng, Sok Meng ;

Erazo, Monica ;

Ostrer, Harry ;

Abraham, Clara ;

Abreu, Maria T. ;

Atzmon, Gil ;

Barzilai, Nir ;

Brant, Steven R. ;

Bressman, Susan ;

Burns, Edward R. ;

Chowers, Yehuda ;

Clark, Lorraine N. ;

Darvasi, Ariel ;

Doheny, Dana ;

Duerr, Richard H. ;

Eliakim, Rami ;

Giladi, Nir ;

Gregersen, Peter K. ;

Hakonarson, Hakon ;

Jones, Michelle R. ;

Marder, Karen ;

McGovern, Dermot P. B. ;

Mulle, Jennifer ;

Orr-Urtreger, Avi ;

Proctor, Deborah D. ;

Pulver, Ann ;

Rotter, Jerome I. ;

Silverberg, Mark S. ;

Ullman, Thomas ;

Warren, Stephen T. ;

Waterman, Matti ;

Zhang, Wei ;

Bergman, Aviv ;

Mayer, Lloyd ;

Katz, Seymour ;

Desnick, Robert J. ;

Cho, Judy H. ;

Peter, Inga .

PLOS GENETICS, 2012, 8 (03)

[92] Profiling of a Prescription Drug Library for Potential Renal Drug-Drug Interactions Mediated by the Organic Cation Transporter 2 [J].

Kido, Yasuto ;

Matsson, Paer ;

Giacomini, Kathleen M. .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (13) :4548-4558

[93] Zinc as a paracrine effector in pancreatic islet cell death [J].

Kim, BJ ;

Kim, YH ;

Kim, S ;

Kim, JW ;

Koh, JY ;

Oh, SH ;

Lee, MK ;

Kim, KW ;

Lee, MS .

DIABETES, 2000, 49 (03) :367-372

[94] DrugBank 3.0: a comprehensive resource for 'Omics' research on drugs [J].

Knox, Craig ;

Law, Vivian ;

Jewison, Timothy ;

Liu, Philip ;

Ly, Son ;

Frolkis, Alex ;

Pon, Allison ;

Banco, Kelly ;

Mak, Christine ;

Neveu, Vanessa ;

Djoumbou, Yannick ;

Eisner, Roman ;

Guo, An Chi ;

Wishart, David S. .

NUCLEIC ACIDS RESEARCH, 2011, 39 :D1035-D1041

[95] The SLC22 drug transporter family [J].

Koepsell, H ;

Endou, H .

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2004, 447 (05) :666-676

[96] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations [J].

Koettgen, Anna ;

Albrecht, Eva ;

Teumer, Alexander ;

Vitart, Veronique ;

Krumsiek, Jan ;

Hundertmark, Claudia ;

Pistis, Giorgio ;

Ruggiero, Daniela ;

O'Seaghdha, Conall M. ;

Haller, Toomas ;

Yang, Qiong ;

Tanaka, Toshiko ;

Johnson, Andrew D. ;

Kutalik, Zoltan ;

Smith, Albert V. ;

Shi, Julia ;

Struchalin, Maksim ;

Middelberg, Rita P. S. ;

Brown, Morris J. ;

Gaffo, Angelo L. ;

Pirastu, Nicola ;

Li, Guo ;

Hayward, Caroline ;

Zemunik, Tatijana ;

Huffman, Jennifer ;

Yengo, Loic ;

Zhao, Jing Hua ;

Demirkan, Ayse ;

Feitosa, Mary F. ;

Liu, Xuan ;

Malerba, Giovanni ;

Lopez, Lorna M. ;

van der Harst, Pim ;

Li, Xinzhong ;

Kleber, Marcus E. ;

Hicks, Andrew A. ;

Nolte, Ilja M. ;

Johansson, Asa ;

Murgia, Federico ;

Wild, Sarah H. ;

Bakker, Stephan J. L. ;

Peden, John F. ;

Dehghan, Abbas ;

Steri, Maristella ;

Tenesa, Albert ;

Lagou, Vasiliki ;

Salo, Perttu ;

Mangino, Massimo ;

Rose, Lynda M. ;

Lehtimaki, Terho .

NATURE GENETICS, 2013, 45 (02) :145-154

[97] Amino Acid Transporter-Targeted Radiotracers for Molecular Imaging in Oncology [J].

Kong, Fan-Lin ;

Yang, David J. .

CURRENT MEDICINAL CHEMISTRY, 2012, 19 (20) :3271-3281

[98] Small-molecule activator of glutamate transporter EAAT2 translation provides neuroprotection [J].

Kong, Qiongman ;

Chang, Ling-Chu ;

Takahashi, Kou ;

Liu, Qibing ;

Schulte, Delanie A. ;

Lai, Liching ;

Ibabao, Brian ;

Lin, Yuchen ;

Stouffer, Nathan ;

Das Mukhopadhyay, Chitra ;

Xing, Xuechao ;

Seyb, Kathleen I. ;

Cuny, Gregory D. ;

Glicksman, Marcie A. ;

Lin, Chien-Liang Glenn .

JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (03) :1255-1267

[99] Mutations in a Thiamine-Transporter Gene and Wernicke's-like Encephalopathy [J].

Kono, Satoshi ;

Miyajima, Hiroaki ;

Yoshida, Kenichi ;

Togawa, Akashi ;

Shirakawa, Kentaro ;

Suzuki, Hitoshi .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (17) :1792-1794

[100] SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation [J].

Kristensen, Anders S. ;

Andersen, Jacob ;

Jorgensen, Trine N. ;

Sorensen, Lena ;

Eriksen, Jacob ;

Loland, Claus J. ;

Stromgaard, Kristian ;

Gether, Ulrik .

PHARMACOLOGICAL REVIEWS, 2011, 63 (03) :585-640

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