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
  • [121] Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets
    Miranda-Goncalves, Vera
    Honavar, Mrinalini
    Pinheiro, Celine
    Martinho, Olga
    Pires, Manuel M.
    Pinheiro, Celia
    Cordeiro, Michelle
    Bebiano, Gil
    Costa, Paulo
    Palmeirim, Isabel
    Reis, Rui M.
    Baltazar, Fatima
    [J]. NEURO-ONCOLOGY, 2013, 15 (02) : 172 - 188
  • [122] Spinal antiallodynia action of glycine transporter inhibitors in neuropathic pain models in mice
    Morita, Katsuya
    Motoyama, Naoyo
    Kitayama, Tomoya
    Morioka, Norimitsu
    Kifune, Koki
    Dohi, Toshihiro
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2008, 326 (02) : 633 - 645
  • [123] The SLC2 (GLUT) family of membrane transporters
    Mueckler, Mike
    Thorens, Bernard
    [J]. MOLECULAR ASPECTS OF MEDICINE, 2013, 34 (2-3) : 121 - 138
  • [124] Monocarboxylate transporter MCT1 is a target for immunosuppression
    Murray, CM
    Hutchinson, R
    Bantick, JR
    Belfield, GP
    Benjamin, AD
    Brazma, D
    Bundick, RV
    Cook, ID
    Craggs, RI
    Edwards, S
    Evans, LR
    Harrison, R
    Holness, E
    Jackson, AP
    Jackson, CG
    Kingston, LP
    Perry, MWD
    Ross, ARJ
    Rugman, PA
    Sidhu, SS
    Sullivan, M
    Taylor-Fishwick, DA
    Walker, PC
    Whitehead, YM
    Wilkinson, DJ
    Wright, A
    Donald, DK
    [J]. NATURE CHEMICAL BIOLOGY, 2005, 1 (07) : 371 - 376
  • [125] Genome-Wide Association Study of Tanning Phenotype in a Population of European Ancestry
    Nan, Hongmei
    Kraft, Peter
    Qureshi, Abrar A.
    Guo, Qun
    Chen, Constance
    Hankinson, Susan E.
    Hu, Frank B.
    Thomas, Gilles
    Hoover, Robert N.
    Chanock, Stephen
    Hunter, David J.
    Han, Jiali
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 (09) : 2250 - 2257
  • [126] L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors
    Nawashiro, Hiroshi
    Otani, Naoki
    Shinomiya, Nariyoshi
    Fukui, Shinji
    Ooigawa, Hidetoshi
    Shima, Katsuji
    Matsuo, Hirotaka
    Kanai, Yoshikatsu
    Endou, Hitoshi
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2006, 119 (03) : 484 - 492
  • [127] Exome sequencing identifies the cause of a mendelian disorder
    Ng, Sarah B.
    Buckingham, Kati J.
    Lee, Choli
    Bigham, Abigail W.
    Tabor, Holly K.
    Dent, Karin M.
    Huff, Chad D.
    Shannon, Paul T.
    Jabs, Ethylin Wang
    Nickerson, Deborah A.
    Shendure, Jay
    Bamshad, Michael J.
    [J]. NATURE GENETICS, 2010, 42 (01) : 30 - U41
  • [128] Nickell JR, 2014, ADV PHARMACOL, V69, P71, DOI 10.1016/B978-0-12-420118-7.00002-0
  • [129] Insulin Storage and Glucose Homeostasis in Mice Null for the Granule Zinc Transporter ZnT8 and Studies of the Type 2 Diabetes-Associated Variants
    Nicolson, Tamara J.
    Bellomo, Elisa A.
    Wijesekara, Nadeeja
    Loder, Merewyn K.
    Baldwin, Jocelyn M.
    Gyulkhandanyan, Armen V.
    Koshkin, Vasilij
    Tarasov, Andrei I.
    Carzaniga, Raffaella
    Kronenberger, Katrin
    Taneja, Tarvinder K.
    Xavier, Gabriela da Silva
    Libert, Sarah
    Froguel, Philippe
    Scharfmann, Raphael
    Stetsyuk, Volodymir
    Ravassard, Philippe
    Parker, Helen
    Gribble, Fiona M.
    Reimann, Frank
    Sladek, Robert
    Hughes, Stephen J.
    Johnson, Paul R. V.
    Masseboeuf, Myriam.
    Burcelin, Remy
    Baldwin, Stephen A.
    Liu, Ming
    Lara-Lemus, Roberto
    Arvan, Peter
    Schuit, Frans C.
    Wheeler, Michael B.
    Chimienti, Fabrice
    Rutter, Guy A.
    [J]. DIABETES, 2009, 58 (09) : 2070 - 2083
  • [130] Occupancy of serotonin and norepinephrine transporter by milnacipran in patients with major depressive disorder: a positron emission tomography study with [11C]DASB and (S,S)-[18F]FMeNER-D2
    Nogami, Tsuyoshi
    Takano, Harumasa
    Arakawa, Ryosuke
    Ichimiya, Tetsuya
    Fujiwara, Hironobu
    Kimura, Yasuyuki
    Kodaka, Fumitoshi
    Sasaki, Takeshi
    Takahata, Keisuke
    Suzuki, Masayuki
    Nagashima, Tomohisa
    Mori, Takaaki
    Shimada, Hitoshi
    Fukuda, Hajime
    Sekine, Mizuho
    Tateno, Amane
    Takahashi, Hidehiko
    Ito, Hiroshi
    Okubo, Yoshiro
    Suhara, Tetsuya
    [J]. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2013, 16 (05) : 937 - 943