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Drug Transporters


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Giacomini KM, Galetin A, Huang SM. The international transporter consortium: summarizing advances in the role of transporters in drug development. Clin Pharmacol Ther 2018; 104(5):766–771.

      39 [39] Chu X, Chan GH, Evers R. Identification of endogenous biomarkers to predict the propensity of drug candidates to cause hepatic or renal transporter‐mediated drug‐drug interactions. J Pharm Sci 2017; 106(9):2357–2367.

      40 [40] Wright SH. Molecular and cellular physiology of organic cation transporter 2. Am J Physiol Renal Physiol 2019; 317(6):F1669–F1679.

      41 [41] Urakami Y, Okuda M, Saito H, Inui K. Hormonal regulation of organic cation transporter OCT2 expression in rat kidney. FEBS Lett 2000; 473(2):173–176.

      42 [42] Jonker JW, Wagenaar E, Van Eijl S, Schinkel AH. Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations. Mol Cell Biol 2003; 23(21):7902–7908.

      43 [43] Ciarimboli G, Deuster D, Knief A, Sperling M, Holtkamp M, Edemir B, Pavenstädt H, Lanvers‐Kaminsky C, Am Zehnhoff‐Dinnesen A, Schinkel AH, Koepsell H, Jürgens H, Schlatter E. Organic cation transporter 2 mediates cisplatin‐induced oto‐ and nephrotoxicity and is a target for protective interventions. Am J Pathol 2010; 176(3):1169–1180.

      44 [44] Leabman MK, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, Deyoung J, Taylor T, Clark AG, Herskowitz I, Giacomini KM, Investigators POMT. Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit altered function. Pharmacogenetics 2002; 12(5):395–405.

      45 [45] Fujita T, Urban TJ, Leabman MK, Fujita K, Giacomini KM. Transport of drugs in the kidney by the human organic cation transporter, OCT2 and its genetic variants. J Pharm Sci 2006; 95(1):25–36.

      46 [46] Zwart R, Verhaagh S, Buitelaar M, Popp‐Snijders C, Barlow DP. Impaired activity of the extraneuronal monoamine transporter system known as uptake‐2 in Orct3/Slc22a3‐deficient mice. Mol Cell Biol 2001; 21(13):4188–4196.

      47 [47] Vollmar J, Lautem A, Closs E, Schuppan D, Kim YO, Grimm D, Marquardt JU, Fuchs P, Straub BK, Schad A, Gründemann D, Schattenberg JM, Gehrke N, Wörns MA, Baumgart J, Galle PR, Zimmermann T. Loss of organic cation transporter 3 (Oct3) leads to enhanced proliferation and hepatocarcinogenesis. Oncotarget 2017; 8(70):115667–115680.

      48 [48] Vialou V, Balasse L, Callebert J, Launay JM, Giros B, Gautron S. Altered aminergic neurotransmission in the brain of organic cation transporter 3‐deficient mice. J Neurochem 2008; 106(3):1471–1482.

      49 [49] Wultsch T, Grimberg G, Schmitt A, Painsipp E, Wetzstein H, Breitenkamp AF, Gründemann D, Schömig E, Lesch KP, Gerlach M, Reif A. Decreased anxiety in mice lacking the organic cation transporter 3. J Neural Transm (Vienna) 2009; 116(6):689–697.

      50 [50] Eeles RA, Kote‐Jarai Z, Giles GG, Olama AA, Guy M, Jugurnauth SK, Mulholland S, Leongamornlert DA, Edwards SM, Morrison J, Field HI, Southey MC, Severi G, Donovan JL, Hamdy FC, Dearnaley DP, Muir KR, Smith C, Bagnato M, Ardern‐Jones AT, Hall AL, O’Brien LT, Gehr‐Swain BN, Wilkinson RA, Cox A, Lewis S, Brown PM, Jhavar SG, Tymrakiewicz M, Lophatananon A, Bryant SL, Horwich A, Huddart RA, Khoo VS, Parker CC, Woodhouse CJ, Thompson A, Christmas T, Ogden C, Fisher C, Jamieson C, Cooper CS, English DR, Hopper JL, Neal DE, Easton DF, Collaborators UGPCS, Oncology BAOUSSO, Collaborators UPS. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet 2008; 40(3):316–321.

      51 [51] Cui R, Okada Y, Jang SG, Ku JL, Park JG, Kamatani Y, Hosono N, Tsunoda T, Kumar V, Tanikawa C, Kamatani N, Yamada R, Kubo M, Nakamura Y, Matsuda K. Common variant in 6q26‐q27 is associated with distal colon cancer in an Asian population. Gut 2011; 60(6):799–805.

      52 [52] Lazar A, Walitza S, Jetter A, Gerlach M, Warnke A, Herpertz‐Dahlmann B, Gründemann D, Grimberg G, Schulz E, Remschmidt H, Wewetzer C, Schömig E. Novel mutations of the extraneuronal monoamine transporter gene in children and adolescents with obsessive‐compulsive disorder. Int J Neuropsychopharmacol 2008; 11(1):35–48.

      53 [53] Eudy JD, Spiegelstein O, Barber RC, Wlodarczyk BJ, Talbot J, Finnell RH. Identification and characterization of the human and mouse SLC19A3 gene: a novel member of the reduced folate family of micronutrient transporter genes. Mol Genet Metab 2000; 71(4):581–590.

      54 [54] Swier LJ, Monjas L, Guskov A, de Voogd AR, Erkens GB, Slotboom DJ, Hirsch AK. Structure‐based design of potent small‐molecule binders to the S‐component of the ECF transporter for thiamine. Chembiochem 2015; 16(5):819–826.

      55 [55] Liang X, Chien HC, Yee SW, Giacomini MM, Chen EC, Piao M, Hao J, Twelves J, Lepist EI, Ray AS, Giacomini KM. Metformin is a substrate and inhibitor of the human thiamine transporter, THTR‐2 (SLC19A3). Mol Pharm 2015; 12(12):4301–4310.

      56 [56] Giacomini MM, Hao J, Liang X, Chandrasekhar J, Twelves J, Whitney JA, Lepist EI, Ray AS. Interaction of 2,4‐diaminopyrimidine‐containing drugs including fedratinib and trimethoprim with thiamine transporters. Drug Metab Dispos 2017; 45(1):76–85.

      57 [57] Zhang Q, Zhang Y, Diamond S, Boer J, Harris JJ, Li Y, Rupar M, Behshad E, Gardiner C, Collier P, Liu P, Burn T, Wynn R, Hollis G, Yeleswaram S. The Janus kinase 2 inhibitor fedratinib inhibits thiamine uptake: a putative mechanism for the onset of Wernicke's encephalopathy. Drug Metab Dispos 2014; 42(10):1656–1662.

      58 [58] Vora B, Green EAE, Khuri N, Ballgren F, Sirota M, Giacomini KM. Drug‐nutrient interactions: discovering prescription drug inhibitors of the thiamine transporter ThTR‐2 (SLC19A3). Am J Clin Nutr 2020; 111(1):110–121.

      59 [59] Mimura Y, Yasujima T, Ohta K, Inoue K, Yuasa H. Functional identification of plasma membrane monoamine transporter (PMAT/SLC29A4) as an atenolol transporter sensitive to flavonoids contained in apple juice. J Pharm Sci 2017; 106(9):2592–2598.

      60 [60] Zhou M, Xia L, Wang J. Metformin transport by a newly cloned proton‐stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metab Dispos 2007; 35(10):1956–1962.

      61 [61] Duan H, Hu T, Foti RS, Pan Y, Swaan PW, Wang J. Potent and selective inhibition of plasma membrane monoamine transporter by HIV protease inhibitors. Drug Metab Dispos 2015; 43(11):1773–1780.

      62 [62] Reidling JC, Lambrecht N, Kassir M, Said HM. Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter‐2‐deficient mice. Gastroenterology 2010; 138(5):1802–1809.

      63 [63] Oishi K, Hofmann S, Diaz GA, Brown T, Manwani D, Ng L, Young R, Vlassara H, Ioannou YA, Forrest D, Gelb BD. Targeted disruption of Slc19a2, the gene encoding the high‐affinity thiamin transporter Thtr‐1, causes diabetes mellitus, sensorineural deafness and megaloblastosis in mice. Hum Mol Genet 2002; 11(23):2951–2960.

      64 [64] Duan H, Wang J. Impaired monoamine and organic cation uptake in choroid plexus in mice with targeted disruption of the plasma membrane monoamine transporter (Slc29a4) gene. J Biol Chem 2013; 288(5):3535–3544.

      65 [65] Gilman TL, George CM, Vitela M, Herrera‐Rosales M, Basiouny MS, Koek W, Daws LC. Constitutive plasma membrane monoamine transporter (PMAT, Slc29a4) deficiency subtly affects anxiety‐like and coping behaviours. Eur J Neurosci 2018; 48(1): 1706–1716.

      66 [66] Wei R, Gust SL, Tandio D, Maheux A, Nguyen KH, Wang J, Bourque S, Plane F, Hammond JR. Deletion of murine slc29a4 modifies vascular responses to adenosine and 5‐hydroxytryptamine in a sexually dimorphic manner. Physiol Rep 2020; 8(5):e14395.

      67 [67] Online Mendelian Inheritance in Man. OMIM® [Internet]. Available at https://omim.org/. Accessed December 3, 2020.

      68 [68] Xian X, Liao L, Shu W, Li H, Qin Y, Yan J, Luo J, Lin FQ. A novel mutation of SLC19A2 in a Chinese Zhuang ethnic family with thiamine‐responsive megaloblastic anemia. Cell Physiol Biochem 2018; 47(5):1989–1997.

      69 [69] Scharfe C, Hauschild M, Klopstock T, Janssen AJ, Heidemann PH, Meitinger T, Jaksch M. A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I. J Med Genet 2000; 37(9):669–673.

      70 [70] Subramanian VS, Marchant JS, Said HM. Biotin‐responsive basal