SLC transporters as therapeutic targets: emerging opportunities

被引:561
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
基金
加拿大健康研究院; 美国国家卫生研究院;
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
收藏
页码:543 / 560
页数:18
相关论文
共 214 条
  • [1] Allosteric Modulation of an Excitatory Amino Acid Transporter: The Subtype-Selective Inhibitor UCPH-101 Exerts Sustained Inhibition of EAAT1 through an Intramonomeric Site in the Trimerization Domain
    Abrahamsen, Bjarke
    Schneider, Nicole
    Erichsen, Mette N.
    Huynh, Tri H. V.
    Fahlke, Christoph
    Bunch, Lennart
    Jensen, Anders A.
    [J]. JOURNAL OF NEUROSCIENCE, 2013, 33 (03) : 1068 - 1087
  • [2] Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: Novel pathways and targets for anticancer therapeutics
    Airley, Rachel E.
    Mobasheri, Ali
    [J]. CHEMOTHERAPY, 2007, 53 (04) : 233 - 256
  • [3] Alasti E, 2014, GENEREVIEWS
  • [4] Urate Transporters: An Evolving Field
    Anzai, Naohiko
    Endou, Hitoshi
    [J]. SEMINARS IN NEPHROLOGY, 2011, 31 (05) : 400 - 409
  • [5] Apical sodium dependent bile acid transporter (ASBT, SLC10A2): A potential prodrug target
    Balakrishnan, Anand
    Polli, James E.
    [J]. MOLECULAR PHARMACEUTICS, 2006, 3 (03) : 223 - 230
  • [6] Bali D.S., 2013, GeneReviews
  • [7] Exome sequencing as a tool for Mendelian disease gene discovery
    Bamshad, Michael J.
    Ng, Sarah B.
    Bigham, Abigail W.
    Tabor, Holly K.
    Emond, Mary J.
    Nickerson, Deborah A.
    Shendure, Jay
    [J]. NATURE REVIEWS GENETICS, 2011, 12 (11) : 745 - 755
  • [8] Mayo Genome Consortia: A Genotype-Phenotype Resource for Genome-Wide Association Studies With an Application to the Analysis of Circulating Bilirubin Levels
    Bielinski, Suzette J.
    Chai, High Seng
    Pathak, Jyotishman
    Talwalkar, Jayant A.
    Limburg, Paul J.
    Gullerud, Rachel E.
    Sicotte, Hugues
    Klee, Eric W.
    Ross, Jason L.
    Kocher, Jean-Pierre A.
    Kullo, Iftikhar J.
    Heit, John A.
    Petersen, Gloria M.
    de Andrade, Mariza
    Chute, Christopher G.
    [J]. MAYO CLINIC PROCEEDINGS, 2011, 86 (07) : 606 - 614
  • [9] Apical transporters for neutral amino acids:: Physiology and pathophysiology
    Broeer, Stefan
    [J]. PHYSIOLOGY, 2008, 23 (02) : 95 - 103
  • [10] Hunting human disease genes: lessons from the past, challenges for the future
    Brunham, Liam R.
    Hayden, Michael R.
    [J]. HUMAN GENETICS, 2013, 132 (06) : 603 - 617