{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:50:36Z","timestamp":1791978636825,"version":"4.4.0"},"reference-count":240,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["dmd.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Metabolism and Disposition"],"published-print":{"date-parts":[[2014,4]]},"DOI":"10.1124\/dmd.113.055723","type":"journal-article","created":{"date-parts":[[2014,1,7]],"date-time":"2014-01-07T02:36:01Z","timestamp":1389062161000},"page":"632-649","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":85,"title":["The Major Facilitative Folate Transporters Solute Carrier 19A1 and Solute Carrier 46A1: Biology and Role in Antifolate Chemotherapy of Cancer"],"prefix":"10.1016","volume":"42","author":[{"given":"Larry H.","family":"Matherly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike R.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanjun","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/dmd.113.055723_bib1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1126\/science.1088196","article-title":"Structure and mechanism of the lactose permease of Escherichia coli","volume":"301","author":"Abramson","year":"2003","journal-title":"Science"},{"key":"10.1124\/dmd.113.055723_bib2","doi-asserted-by":"crossref","first-page":"6478","DOI":"10.1016\/S0021-9258(19)84587-8","article-title":"The effect of methotrexate on intracellular folate pools in human MCF-7 breast cancer cells. Evidence for direct inhibition of purine synthesis","volume":"261","author":"Allegra","year":"1986","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib3","doi-asserted-by":"crossref","unstructured":"Alvarez-Fernandez C Perez-Arnillas Q Ruiz-Echeverria L Rodriguez-Rubi D Sanchez-Lorenzo L Li-Torres W Izquierdo-Manuel M Berros JP Luque-Cabal M Jimenez-Fonseca P Reduced folate carrier (RFC) as a predictive marker for response to pemetrexed in advanced non-small cell lung cancer (NSCLC) Invest New Drugs 2013 [published ahead of print] et al","DOI":"10.1007\/s10637-013-9992-1"},{"key":"10.1124\/dmd.113.055723_bib4","doi-asserted-by":"crossref","first-page":"614","DOI":"10.3109\/08880018.2010.481705","article-title":"Mutation of the proton-coupled folate transporter gene (PCFT-SLC46A1) in Turkish siblings with hereditary folate malabsorption","volume":"27","author":"Atabay","year":"2010","journal-title":"Pediatr Hematol Oncol"},{"key":"10.1124\/dmd.113.055723_bib5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S0021-9258(17)31261-9","article-title":"A new folate antimetabolite, 5,10-dideaza-5,6,7,8-tetrahydrofolate is a potent inhibitor of de novo purine synthesis","volume":"264","author":"Beardsley","year":"1989","journal-title":"J Biol Chem"},{"issue":"15","key":"10.1124\/dmd.113.055723_bib6","doi-asserted-by":"crossref","first-page":"5487","DOI":"10.1158\/1078-0432.CCR-05-0104","article-title":"Phase I study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor in patients with refractory solid tumors","volume":"11","author":"Beutel","year":"2005","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1054\/bjoc.2000.1601","article-title":"Phase I dose-escalation and pharmacokinetic study of a novel folate analogue AG2034","volume":"84","author":"Bissett","year":"2001","journal-title":"Br J Cancer"},{"key":"10.1124\/dmd.113.055723_bib8","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF00194533","article-title":"AG2034: a novel inhibitor of glycinamide ribonucleotide formyltransferase","volume":"14","author":"Boritzki","year":"1996","journal-title":"Invest New Drugs"},{"key":"10.1124\/dmd.113.055723_bib9","doi-asserted-by":"crossref","unstructured":"Brandsch C Zibolka J Frommhagen M Lehmann U Dierkes J K\u00fchne H Hirche F Stangl GI Vitamin D is not linked to folate status and mRNA expression of intestinal proton-coupled folate transporter Eur J Nutr 2013 [published ahead of print]","DOI":"10.1007\/s00394-013-0614-7"},{"key":"10.1124\/dmd.113.055723_bib10","doi-asserted-by":"crossref","first-page":"22974","DOI":"10.1074\/jbc.270.39.22974","article-title":"Characterization of a mutation in the reduced folate carrier in a transport defective L1210 murine leukemia cell line","volume":"270","author":"Brigle","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib11","doi-asserted-by":"crossref","first-page":"48861","DOI":"10.1074\/jbc.M304844200","article-title":"A defect in the p53 response pathway induced by de novo purine synthesis inhibition","volume":"278","author":"Bronder","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib12","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s002800000272","article-title":"Phase I and pharmacokinetic study of LY309887: a specific inhibitor of purine biosynthesis","volume":"47","author":"Budman","year":"2001","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib13","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.pharmthera.2012.07.010","article-title":"Drug transport by Organic Anion Transporters (OATs)","volume":"136","author":"Burckhardt","year":"2012","journal-title":"Pharmacol Ther"},{"key":"10.1124\/dmd.113.055723_bib14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1042\/bj20030301","article-title":"Characterization of a cysteine-less human reduced folate carrier: localization of a substrate-binding domain by cysteine-scanning mutagenesis and cysteine accessibility methods","volume":"374","author":"Cao","year":"2003","journal-title":"Biochem J"},{"key":"10.1124\/dmd.113.055723_bib15","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1212\/WNL.0b013e3181c679df","article-title":"Congenital null mutations of the FOLR1 gene: a progressive neurologic disease and its treatment","volume":"73","author":"Cario","year":"2009","journal-title":"Neurology"},{"key":"10.1124\/dmd.113.055723_bib16","doi-asserted-by":"crossref","first-page":"20676","DOI":"10.1074\/jbc.M002328200","article-title":"Expression and differential polarization of the reduced-folate transporter-1 and the folate receptor alpha in mammalian retinal pigment epithelium","volume":"275","author":"Chancy","year":"2000","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib17","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/09687680410001720830","article-title":"Phylogeny as a guide to structure and function of membrane transport proteins","volume":"21","author":"Chang","year":"2004","journal-title":"Mol Membr Biol"},{"key":"10.1124\/dmd.113.055723_bib18","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1158\/1535-7163.MCT-06-0343","article-title":"Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications","volume":"6","author":"Chattopadhyay","year":"2007","journal-title":"Mol Cancer Ther"},{"key":"10.1124\/dmd.113.055723_bib19","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/0006-2952(82)90376-8","article-title":"Further studies stereospecificity at carbon 6 for membrane transport of tetrahydrofolates. Diastereoisomers of 5-methyltetrahydrofolates as competitive inhibitors of transport of methotrexate in L1210 cells","volume":"31","author":"Chello","year":"1982","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib20","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s00280-013-2094-0","article-title":"Therapeutic targeting malignant mesothelioma with a novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate via its selective uptake by the proton-coupled folate transporter","volume":"71","author":"Cherian","year":"2013","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib21","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s002280050404","article-title":"Pharmacokinetics of low doses of methotrexate in patients with psoriasis over the early period of treatment","volume":"53","author":"Chl\u00e1dek","year":"1998","journal-title":"Eur J Clin Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib22","doi-asserted-by":"crossref","first-page":"S80","DOI":"10.1007\/s00280-003-0625-9","article-title":"Thymidylate synthase inhibitors as anticancer agents: from bench to bedside","volume":"52","author":"Chu","year":"2003","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib23","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s10637-007-9040-0","article-title":"A randomised phase II study of OSI-7904L versus 5-fluorouracil (FU)\/leucovorin (LV) as first-line treatment in patients with advanced biliary cancers","volume":"25","author":"Ciuleanu","year":"2007","journal-title":"Invest New Drugs"},{"key":"10.1124\/dmd.113.055723_bib24","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00280-007-0509-5","article-title":"A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer","volume":"61","author":"Clamp","year":"2008","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib25","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1634\/theoncologist.2010-0224","article-title":"Approval summary: pemetrexed maintenance therapy of advanced\/metastatic nonsquamous, non-small cell lung cancer (NSCLC)","volume":"15","author":"Cohen","year":"2010","journal-title":"Oncologist"},{"key":"10.1124\/dmd.113.055723_bib26","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1634\/theoncologist.2009-0092","article-title":"Approval summary: pemetrexed in the initial treatment of advanced\/metastatic non-small cell lung cancer","volume":"14","author":"Cohen","year":"2009","journal-title":"Oncologist"},{"key":"10.1124\/dmd.113.055723_bib27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00280-007-0576-7","article-title":"Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia","volume":"62","author":"Cole","year":"2008","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib28","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1124\/mol.107.043190","article-title":"Role of lysine 411 in substrate carboxyl group binding to the human reduced folate carrier, as determined by site-directed mutagenesis and affinity inhibition","volume":"73","author":"Deng","year":"2008","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib29","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1021\/jm8011323","volume":"52","author":"Deng","year":"2009","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib30","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.4161\/cbt.22020","article-title":"The human proton-coupled folate transporter: Biology and therapeutic applications to cancer","volume":"13","author":"Desmoulin","year":"2012","journal-title":"Cancer Biol Ther"},{"key":"10.1124\/dmd.113.055723_bib31","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1124\/mol.112.079004","article-title":"Functional loss of the reduced folate carrier enhances the antitumor activities of novel antifolates with selective uptake by the proton-coupled folate transporter","volume":"82","author":"Desmoulin","year":"2012","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib32","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1124\/mol.110.065896","article-title":"Targeting the proton-coupled folate transporter for selective delivery of 6-substituted pyrrolo[2,3-d]pyrimidine antifolate inhibitors of de novo purine biosynthesis in the chemotherapy of solid tumors","volume":"78","author":"Desmoulin","year":"2010","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib33","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.gene.2013.06.039","article-title":"A novel deletion mutation in the proton-coupled folate transporter (PCFT; SLC46A1) in a Nicaraguan child with hereditary folate malabsorption","volume":"527","author":"Diop-Bove","year":"2013","journal-title":"Gene"},{"key":"10.1124\/dmd.113.055723_bib34","series-title":"GeneReviews","article-title":"Hereditary Folate Malabsorption","author":"Diop-Bove","year":"2008"},{"key":"10.1124\/dmd.113.055723_bib35","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1158\/1535-7163.MCT-08-0938","article-title":"Hypermethylation of the human proton-coupled folate transporter (SLC46A1) minimal transcriptional regulatory region in an antifolate-resistant HeLa cell line","volume":"8","author":"Diop-Bove","year":"2009","journal-title":"Mol Cancer Ther"},{"key":"10.1124\/dmd.113.055723_bib36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0021-9258(17)42301-5","article-title":"A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells","volume":"269","author":"Dixon","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib37","doi-asserted-by":"crossref","first-page":"30855","DOI":"10.1074\/jbc.M003988200","article-title":"Clustering of mutations in the first transmembrane domain of the human reduced folate carrier in GW1843U89-resistant leukemia cells with impaired antifolate transport and augmented folate uptake","volume":"275","author":"Drori","year":"2000","journal-title":"J Biol Chem"},{"issue":"3","key":"10.1124\/dmd.113.055723_bib38","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1046\/j.1432-1327.2000.01049.x","article-title":"Characterization of a human alternatively spliced truncated reduced folate carrier increasing folate accumulation in parental leukemia cells","volume":"267","author":"Drori","year":"2000","journal-title":"Eur J Biochem"},{"key":"10.1124\/dmd.113.055723_bib39","first-page":"1","article-title":"Mutational analysis of the role of GXXXG motif in the function of human organic anion transporter 1 (hOAT1)","volume":"2","author":"Duan","year":"2011","journal-title":"Int J Biochem Mol Biol"},{"key":"10.1124\/dmd.113.055723_bib40","first-page":"810","article-title":"Biochemical and cellular pharmacology of 1843U89, a novel benzoquinazoline inhibitor of thymidylate synthase","volume":"53","author":"Duch","year":"1993","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib41","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1111\/febs.12293","article-title":"The monomeric state of the proton-coupled folate transporter represents the functional unit in the plasma membrane","volume":"280","author":"Duddempudi","year":"2013","journal-title":"FEBS J"},{"key":"10.1124\/dmd.113.055723_bib42","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.addr.2004.01.001","article-title":"Distribution, functionality and gene regulation of folate receptor isoforms: implications in targeted therapy","volume":"56","author":"Elnakat","year":"2004","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1124\/dmd.113.055723_bib43","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1124\/mol.109.055392","article-title":"Vitamin D3 and its nuclear receptor increase the expression and activity of the human proton-coupled folate transporter","volume":"76","author":"Eloranta","year":"2009","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib44","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/sj.bjc.6603267","article-title":"Multicentre phase II pharmacokinetic and pharmacodynamic study of OSI-7904L in previously untreated patients with advanced gastric or gastroesophageal junction adenocarcinoma","volume":"95","author":"Falk","year":"2006","journal-title":"Br J Cancer"},{"key":"10.1124\/dmd.113.055723_bib45","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1182\/blood.V4.2.160.160","article-title":"Some observations on the effect of folic acid antagonists on acute leukemia and other forms of incurable cancer","volume":"4","author":"Farber","year":"1949","journal-title":"Blood"},{"key":"10.1124\/dmd.113.055723_bib46","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1126\/science.106.2764.619","article-title":"The Action of Pteroylglutamic Conjugates on Man","volume":"106","author":"Farber","year":"1947","journal-title":"Science"},{"key":"10.1124\/dmd.113.055723_bib47","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJM194806032382301","article-title":"Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid","volume":"238","author":"Farber","year":"1948","journal-title":"N Engl J Med"},{"key":"10.1124\/dmd.113.055723_bib48","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1056\/NEJM199502023320503","article-title":"Methotrexate for the treatment of Crohn\u2019s disease","volume":"332","author":"Feagan","year":"1995","journal-title":"N Engl J Med"},{"key":"10.1124\/dmd.113.055723_bib49","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/j.1365-2141.2004.05109.x","article-title":"Aberrant methylation in the promoter region of the reduced folate carrier gene is a potential mechanism of resistance to methotrexate in primary central nervous system lymphomas","volume":"126","author":"Ferreri","year":"2004","journal-title":"Br J Haematol"},{"issue":"15","key":"10.1124\/dmd.113.055723_bib50","doi-asserted-by":"crossref","first-page":"5111","DOI":"10.1158\/1078-0432.CCR-04-0116","article-title":"Primary acute lymphoblastic leukemia cells use a novel promoter and 5\u2032noncoding exon for the human reduced folate carrier that encodes a modified carrier translated from an upstream translational start","volume":"10","author":"Flatley","year":"2004","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib51","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.bbrc.2013.01.004","article-title":"Transcriptional regulation of PCFT by KLF4, HNF4\u03b1, CDX2 and C\/EBP\u03b1: implication in its site-specific expression in the small intestine","volume":"431","author":"Furumiya","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1124\/dmd.113.055723_bib52","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/nature07017","article-title":"Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate","volume":"453","author":"Gallagher","year":"2008","journal-title":"Nature"},{"key":"10.1124\/dmd.113.055723_bib53","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/00005792-200201000-00004","article-title":"Hereditary folate malabsorption: family report and review of the literature","volume":"81","author":"Geller","year":"2002","journal-title":"Medicine (Baltimore)"},{"key":"10.1124\/dmd.113.055723_bib54","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/jmri.10181","article-title":"MRI of the tumor microenvironment","volume":"16","author":"Gillies","year":"2002","journal-title":"J Magn Reson Imaging"},{"key":"10.1124\/dmd.113.055723_bib55","first-page":"1657","article-title":"A quantitative comparison of the antileukemic effectiveness of two folic acid antagonists in mice","volume":"15","author":"Goldin","year":"1955","journal-title":"J Natl Cancer Inst"},{"key":"10.1124\/dmd.113.055723_bib56","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1016\/S0021-9258(17)36418-9","article-title":"Transport energetics of the folic acid analogue, methotrexate, in L1210 leukemia cells. Enhanced accumulation by metabolic inhibitors","volume":"244","author":"Goldman","year":"1969","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib57","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1749-6632.1971.tb31167.x","article-title":"The characteristics of the membrane transport of amethopterin and the naturally occurring folates","volume":"186","author":"Goldman","year":"1971","journal-title":"Ann N Y Acad Sci"},{"key":"10.1124\/dmd.113.055723_bib58","doi-asserted-by":"crossref","first-page":"5007","DOI":"10.1016\/S0021-9258(18)91984-8","article-title":"Carrier-mediated transport of the folic acid analogue, methotrexate, in the L1210 leukemia cell","volume":"243","author":"Goldman","year":"1968","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib59","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0163-7258(85)90083-X","article-title":"The cellular pharmacology of methotrexate","volume":"28","author":"Goldman","year":"1985","journal-title":"Pharmacol Ther"},{"key":"10.1124\/dmd.113.055723_bib60","doi-asserted-by":"crossref","first-page":"33602","DOI":"10.1074\/jbc.M110.135640","article-title":"The obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1","volume":"285","author":"Gonen","year":"2010","journal-title":"J Biol Chem"},{"issue":"4","key":"10.1124\/dmd.113.055723_bib61","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.drup.2012.07.002","article-title":"Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance","volume":"15","author":"Gonen","year":"2012","journal-title":"Drug Resist Updat"},{"key":"10.1124\/dmd.113.055723_bib62","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.bbrc.2008.09.074","article-title":"PCFT\/SLC46A1 promoter methylation and restoration of gene expression in human leukemia cells","volume":"376","author":"Gonen","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1124\/dmd.113.055723_bib63","series-title":"The bioavailability of folate","author":"Gregory","year":"1995"},{"key":"10.1124\/dmd.113.055723_bib64","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","article-title":"AMPK phosphorylation of raptor mediates a metabolic checkpoint","volume":"30","author":"Gwinn","year":"2008","journal-title":"Mol Cell"},{"key":"10.1124\/dmd.113.055723_bib65","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1097\/00001813-200305001-00003","article-title":"A review of phase II studies of ZD9331 treatment for relapsed or refractory solid tumours","volume":"14","author":"Hainsworth","year":"2003","journal-title":"Anticancer Drugs"},{"key":"10.1124\/dmd.113.055723_bib66","first-page":"3301","article-title":"In vitro uptake, anabolism, and cellular retention of 1843U89 and other benzoquinazoline inhibitors of thymidylate synthase","volume":"56","author":"Hanlon","year":"1996","journal-title":"Cancer Res"},{"issue":"3","key":"10.1124\/dmd.113.055723_bib67","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1158\/1078-0432.982.11.3","article-title":"Pemetrexed in malignant pleural mesothelioma","volume":"11","author":"Hazarika","year":"2005","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib68","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/0003-9861(83)90162-5","article-title":"Structural requirements for anion substrates of the methotrexate transport system in L1210 cells","volume":"221","author":"Henderson","year":"1983","journal-title":"Arch Biochem Biophys"},{"key":"10.1124\/dmd.113.055723_bib69","doi-asserted-by":"crossref","first-page":"4732","DOI":"10.1074\/jbc.M109.086033","article-title":"Identification of the minimal functional unit of the homo-oligomeric human reduced folate carrier","volume":"285","author":"Hou","year":"2010","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib70","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.1074\/jbc.M111.306860","article-title":"Identification and functional impact of homo-oligomers of the human proton-coupled folate transporter","volume":"287","author":"Hou","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib71","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1074\/jbc.M807206200","article-title":"Oligomeric structure of the human reduced folate carrier: identification of homo-oligomers and dominant-negative effects on carrier expression and function","volume":"284","author":"Hou","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib72","first-page":"212","article-title":"Acute Regulation of Human Reduced Folate Carrier by Folates as a Novel Adaptive Mechanism to Folate Deprivation","volume":"54","author":"Hou","year":"2013","journal-title":"Proceedings AACR"},{"key":"10.1124\/dmd.113.055723_bib73","doi-asserted-by":"crossref","first-page":"36206","DOI":"10.1074\/jbc.M507295200","article-title":"Localization of a substrate binding domain of the human reduced folate carrier to transmembrane domain 11 by radioaffinity labeling and cysteine-substituted accessibility methods","volume":"280","author":"Hou","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib74","doi-asserted-by":"crossref","first-page":"33588","DOI":"10.1074\/jbc.M607049200","article-title":"Transmembrane domains 4, 5, 7, 8, and 10 of the human reduced folate carrier are important structural or functional components of the transmembrane channel for folate substrates","volume":"281","author":"Hou","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib75","first-page":"945","article-title":"Thymidine and hypoxanthine requirements of normal and malignant human cells for protection against methotrexate cytotoxicity","volume":"41","author":"Howell","year":"1981","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib76","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1126\/science.1087619","article-title":"Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli","volume":"301","author":"Huang","year":"2003","journal-title":"Science"},{"key":"10.1124\/dmd.113.055723_bib77","series-title":"Anticancer Drug Development Guide: Antifolate Drugs in Cancer Therapy","first-page":"147","article-title":"Raltitrexed (Tomudex), a Highly Polyglutamatable Antifolate Thymidylate Synthase Inhibitor","author":"Hughes","year":"1999"},{"key":"10.1124\/dmd.113.055723_bib78","doi-asserted-by":"crossref","first-page":"20687","DOI":"10.1074\/jbc.M802812200","article-title":"The reduced folate carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivation. RFC as a double edged sword in folate homeostasis","volume":"283","author":"Ifergan","year":"2008","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib79","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(03)00929-2","article-title":"TSC2 mediates cellular energy response to control cell growth and survival","volume":"115","author":"Inoki","year":"2003","journal-title":"Cell"},{"key":"10.1124\/dmd.113.055723_bib80","doi-asserted-by":"crossref","first-page":"G660","DOI":"10.1152\/ajpgi.00309.2007","article-title":"Functional characterization of PCFT\/HCP1 as the molecular entity of the carrier-mediated intestinal folate transport system in the rat model","volume":"294","author":"Inoue","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"9","key":"10.1124\/dmd.113.055723_bib81","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/oxfordjournals.annonc.a059353","article-title":"Folate-based thymidylate synthase inhibitors as anticancer drugs","volume":"6","author":"Jackman","year":"1995","journal-title":"Ann Oncol"},{"issue":"6","key":"10.1124\/dmd.113.055723_bib82","first-page":"911","article-title":"Cellular pharmacology and in vivo activity of a new anticancer agent, ZD9331: a water-soluble, nonpolyglutamatable, quinazoline-based inhibitor of thymidylate synthase","volume":"3","author":"Jackman","year":"1997","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib83","first-page":"5579","article-title":"ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study","volume":"51","author":"Jackman","year":"1991","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib84","series-title":"Nucleosides and Cancer Treatment","first-page":"18","article-title":"The contributions of de-novo and salvage pathways of nucleotide biosynthesis in normal and malignant cells","author":"Jackson","year":"1981"},{"key":"10.1124\/dmd.113.055723_bib85","series-title":"Anticancer Drug Development Guide: Antifolate Drugs in Cancer Therapy","first-page":"293","article-title":"Receptor- and carrier- mediated transport system for folates and antifolates","author":"Jansen","year":"1999"},{"key":"10.1124\/dmd.113.055723_bib86","doi-asserted-by":"crossref","first-page":"30189","DOI":"10.1074\/jbc.273.46.30189","article-title":"A structurally altered human reduced folate carrier with increased folic acid transport mediates a novel mechanism of antifolate resistance","volume":"273","author":"Jansen","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib87","doi-asserted-by":"crossref","first-page":"18272","DOI":"10.1016\/S0021-9258(17)44748-X","article-title":"Methotrexate transport in variant human CCRF-CEM leukemia cells with elevated levels of the reduced folate carrier. Selective effect on carrier-mediated transport of physiological concentrations of reduced folates","volume":"265","author":"Jansen","year":"1990","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib88","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1124\/pr.113.007518","article-title":"Transporters and drug-drug interactions: important determinants of drug disposition and effects","volume":"65","author":"K\u00f6nig","year":"2013","journal-title":"Pharmacol Rev"},{"issue":"6","key":"10.1124\/dmd.113.055723_bib89","first-page":"2072","article-title":"10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with previously treated non-small cell lung cancer","volume":"9","author":"Krug","year":"2003","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib90","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10555-007-9039-1","article-title":"Physiological and pharmacological functions of Mrp2, Mrp3 and Mrp4 as determined from recent studies on gene-disrupted mice","volume":"26","author":"Kruh","year":"2007","journal-title":"Cancer Metastasis Rev"},{"key":"10.1124\/dmd.113.055723_bib91","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1124\/mol.111.073833","article-title":"Therapeutic targeting of a novel 6-substituted pyrrolo [2,3-d]pyrimidine thienoyl antifolate to human solid tumors based on selective uptake by the proton-coupled folate transporter","volume":"80","author":"Kugel Desmoulin","year":"2011","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib92","doi-asserted-by":"crossref","first-page":"6226","DOI":"10.1074\/jbc.272.10.6226","article-title":"A protein-tyrosine kinase-regulated, pH-dependent, carrier-mediated uptake system for folate in human normal colonic epithelial cell line NCM460","volume":"272","author":"Kumar","year":"1997","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib93","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1182\/blood-2008-04-150276","article-title":"A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function","volume":"112","author":"Lasry","year":"2008","journal-title":"Blood"},{"key":"10.1124\/dmd.113.055723_bib94","doi-asserted-by":"crossref","first-page":"5588","DOI":"10.1074\/jbc.M412662200","article-title":"Structure and regulation of the murine reduced folate carrier gene: identification of four noncoding exons and promoters and regulation by dietary folates","volume":"280","author":"Liu","year":"2005","journal-title":"J Biol Chem"},{"issue":"2","key":"10.1124\/dmd.113.055723_bib95","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1158\/1078-0432.CCR-05-1954","article-title":"Transcriptional regulation of the human reduced folate carrier in childhood acute lymphoblastic leukemia cells","volume":"12","author":"Liu","year":"2006","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib96","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1042\/bj3580511","article-title":"Functional interactions between arginine-133 and aspartate-88 in the human reduced folate carrier: evidence for a charge-pair association","volume":"358","author":"Liu","year":"2001","journal-title":"Biochem J"},{"key":"10.1124\/dmd.113.055723_bib97","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1042\/bj20020419","article-title":"Restoration of high-level transport activity by human reduced folate carrier\/ThTr1 thiamine transporter chimaeras: role of the transmembrane domain 6\/7 linker region in reduced folate carrier function","volume":"369","author":"Liu","year":"2003","journal-title":"Biochem J"},{"key":"10.1124\/dmd.113.055723_bib98","first-page":"279","article-title":"A phase I-II, dose-escalating trial of ZD9331 in combination with irinotecan (CPT11) in previously pretreated metastatic colorectal cancer patients","volume":"91","author":"Louvet","year":"2004","journal-title":"Bull Cancer"},{"key":"10.1124\/dmd.113.055723_bib99","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S1357-2725(99)00139-9","article-title":"S-Adenosylmethionine","volume":"32","author":"Lu","year":"2000","journal-title":"Int J Biochem Cell Biol"},{"key":"10.1124\/dmd.113.055723_bib100","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1006\/mgme.2000.3027","article-title":"Folic acid: nutritional biochemistry, molecular biology, and role in disease processes","volume":"71","author":"Lucock","year":"2000","journal-title":"Mol Genet Metab"},{"issue":"4","key":"10.1124\/dmd.113.055723_bib101","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.jpeds.2011.03.005","article-title":"Prevalence of a loss-of-function mutation in the proton-coupled folate transporter gene (PCFT-SLC46A1) causing hereditary folate malabsorption in Puerto Rico","volume":"159","author":"Mahadeo","year":"2011","journal-title":"J Pediatr"},{"key":"10.1124\/dmd.113.055723_bib102","doi-asserted-by":"crossref","first-page":"C1153","DOI":"10.1152\/ajpcell.00113.2010","article-title":"Properties of the Arg376 residue of the proton-coupled folate transporter (PCFT-SLC46A1) and a glutamine mutant causing hereditary folate malabsorption","volume":"299","author":"Mahadeo","year":"2010","journal-title":"Am J Physiol Cell Physiol"},{"issue":"5","key":"10.1124\/dmd.113.055723_bib103","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1097\/JTO.0b013e318287c224","article-title":"Reduced folate carrier and folylpolyglutamate synthetase, but not thymidylate synthase predict survival in pemetrexed-treated patients suffering from malignant pleural mesothelioma","volume":"8","author":"Mairinger","year":"2013","journal-title":"J Thorac Oncol"},{"key":"10.1124\/dmd.113.055723_bib104","doi-asserted-by":"crossref","first-page":"33325","DOI":"10.1074\/jbc.M205955200","article-title":"Intracellular trafficking and membrane targeting mechanisms of the human reduced folate carrier in Mammalian epithelial cells","volume":"277","author":"Marchant","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib105","doi-asserted-by":"crossref","first-page":"6657","DOI":"10.1158\/1078-0432.CCR-12-2251","article-title":"Pralatrexate pharmacology and clinical development","volume":"19","author":"Marchi","year":"2013","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib106","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1016\/0006-2952(93)90608-Y","article-title":"Determinants of the disparate antitumor activities of (6R)-5,10-dideaza-5,6,7,8-tetrahydrofolate and methotrexate toward human lymphoblastic leukemia cells, characterized by severely impaired antifolate membrane transport","volume":"46","author":"Matherly","year":"1993","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib107","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S0021-9258(19)75842-6","article-title":"The effects on 4-aminoantifolates on 5-formyltetrahydrofolate metabolism in L1210 cells. A biochemical basis of the selectivity of leucovorin rescue","volume":"262","author":"Matherly","year":"1987","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib108","first-page":"3420","article-title":"Identification of a highly glycosylated methotrexate membrane carrier in K562 human erythroleukemia cells up-regulated for tetrahydrofolate cofactor and methotrexate transport","volume":"51","author":"Matherly","year":"1991","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib109","series-title":"Targeted Drug Strategies for Cancer and Inflammation","first-page":"119","article-title":"Discovery of novel antifolate inhibitors of de novo purine nucleotide biosynthesis with selectivity for high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier for cellular entry","author":"Matherly","year":"2011"},{"key":"10.1124\/dmd.113.055723_bib110","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0083-6729(03)01012-4","article-title":"Membrane transport of folates","volume":"66","author":"Matherly","year":"2003","journal-title":"Vitam Horm"},{"key":"10.1124\/dmd.113.055723_bib111","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0083-6729(08)00405-6","article-title":"Structure and function of the reduced folate carrier a paradigm of a major facilitator superfamily mammalian nutrient transporter","volume":"79","author":"Matherly","year":"2008","journal-title":"Vitam Horm"},{"key":"10.1124\/dmd.113.055723_bib112","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10555-007-9046-2","article-title":"Human reduced folate carrier: translation of basic biology to cancer etiology and therapy","volume":"26","author":"Matherly","year":"2007","journal-title":"Cancer Metastasis Rev"},{"key":"10.1124\/dmd.113.055723_bib113","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1016\/0006-2952(90)90622-R","article-title":"Evidence for a localized conversion of endogenous tetrahydrofolate cofactors to dihydrofolate as an important element in antifolate action in murine leukemia cells","volume":"39","author":"Matherly","year":"1990","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib114","first-page":"1073","article-title":"Enhanced polyglutamylation of aminopterin relative to methotrexate in the Ehrlich ascites tumor cell in vitro","volume":"45","author":"Matherly","year":"1985","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib115","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.1158\/0008-5472.CAN-05-3226","article-title":"5-amino-4-imidazolecarboxamide riboside potentiates both transport of reduced folates and antifolates by the human reduced folate carrier and their subsequent metabolism","volume":"66","author":"McGuire","year":"2006","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib116","series-title":"Anticancer Drug Development Guide: Antifolate Drugs in Cancer Therapy","first-page":"261","article-title":"Preclinical and Clinical Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitors Lometrexol and LY309887","author":"Mendelsohn","year":"1999"},{"key":"10.1124\/dmd.113.055723_bib117","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1124\/jpet.112.195479","article-title":"Intestinal transport of aminopterin enantiomers in dogs and humans with psoriasis is stereoselective: evidence for a mechanism involving the proton-coupled folate transporter","volume":"342","author":"Menter","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.113.055723_bib118","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ymgme.2009.11.004","article-title":"A novel PCFT gene mutation (p.Cys66LeufsX99) causing hereditary folate malabsorption","volume":"99","author":"Meyer","year":"2010","journal-title":"Mol Genet Metab"},{"key":"10.1124\/dmd.113.055723_bib119","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.jpeds.2008.04.009","article-title":"The clinical course and genetic defect in the PCFT gene in a 27-year-old woman with hereditary folate malabsorption","volume":"153","author":"Min","year":"2008","journal-title":"J Pediatr"},{"key":"10.1124\/dmd.113.055723_bib120","doi-asserted-by":"crossref","first-page":"10016","DOI":"10.1021\/jm401328u","volume":"56","author":"Mitchell-Ryan","year":"2013","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib121","first-page":"352","article-title":"Similar specificity of membrane transport for folate analogues and their metabolites by murine and human tumor cells: a clinically directed laboratory study","volume":"44","author":"Moccio","year":"1984","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib122","series-title":"Antifolates","author":"Monahan","year":"2011"},{"issue":"2","key":"10.1124\/dmd.113.055723_bib123","first-page":"24","article-title":"Roles of folylpoly-gamma-glutamate synthetase in therapeutics with tetrahydrofolate antimetabolites: an overview","volume":"26","author":"Moran","year":"1999","journal-title":"Semin Oncol"},{"key":"10.1124\/dmd.113.055723_bib124","doi-asserted-by":"crossref","first-page":"21047","DOI":"10.1016\/S0021-9258(19)30043-2","article-title":"The 6S- and 6R-diastereomers of 5, 10-dideaza-5, 6, 7, 8-tetrahydrofolate are equiactive inhibitors of de novo purine synthesis","volume":"264","author":"Moran","year":"1989","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib125","first-page":"3790","article-title":"Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis of its expression in transport-deficient, methotrexate-resistant human breast cancer cells","volume":"55","author":"Moscow","year":"1995","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib126","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1124\/jpet.107.122606","article-title":"Functional characterization of human proton-coupled folate transporter\/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter","volume":"322","author":"Nakai","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.113.055723_bib127","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.bcp.2012.01.002","article-title":"Role of breast cancer resistance protein (BCRP\/ABCG2) in cancer drug resistance","volume":"83","author":"Natarajan","year":"2012","journal-title":"Biochem Pharmacol"},{"issue":"26","key":"10.1124\/dmd.113.055723_bib128","doi-asserted-by":"crossref","first-page":"4357","DOI":"10.1200\/JCO.2008.20.8470","article-title":"Phase II-I-II study of two different doses and schedules of pralatrexate, a high-affinity substrate for the reduced folate carrier, in patients with relapsed or refractory lymphoma reveals marked activity in T-cell malignancies","volume":"27","author":"O'Connor","year":"2009","journal-title":"J Clin Oncol"},{"key":"10.1124\/dmd.113.055723_bib129","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1182\/blood.V100.2.594","article-title":"Strategy for the treatment of acute myelogenous leukemia based on folate receptor beta-targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid","volume":"100","author":"Pan","year":"2002","journal-title":"Blood"},{"key":"10.1124\/dmd.113.055723_bib130","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.bbaexp.2006.12.006","article-title":"Effects of 5\u2032 untranslated region diversity on the posttranscriptional regulation of the human reduced folate carrier","volume":"1769","author":"Payton","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"10.1124\/dmd.113.055723_bib131","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1021\/bi902085q","article-title":"Mutational analysis of threonine 402 adjacent to the GXXXG dimerization motif in transmembrane segment 1 of ABCG2","volume":"49","author":"Polgar","year":"2010","journal-title":"Biochemistry"},{"key":"10.1124\/dmd.113.055723_bib132","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1006\/bbrc.1995.1096","article-title":"Molecular cloning of the human placental folate transporter","volume":"206","author":"Prasad","year":"1995","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1124\/dmd.113.055723_bib133","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.cell.2006.09.041","article-title":"Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption","volume":"127","author":"Qiu","year":"2006","journal-title":"Cell"},{"key":"10.1124\/dmd.113.055723_bib134","doi-asserted-by":"crossref","first-page":"C1669","DOI":"10.1152\/ajpcell.00202.2007","article-title":"Rodent intestinal folate transporters (SLC46A1): secondary structure, functional properties, and response to dietary folate restriction","volume":"293","author":"Qiu","year":"2007","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1124\/dmd.113.055723_bib135","doi-asserted-by":"crossref","first-page":"5467","DOI":"10.1158\/0008-5472.CAN-08-4979","article-title":"Therapeutics by cytotoxic metabolite accumulation: pemetrexed causes ZMP accumulation, AMPK activation, and mammalian target of rapamycin inhibition","volume":"69","author":"Racanelli","year":"2009","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib136","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0090-8258(03)00491-8","article-title":"A phase II study to determine the efficacy and tolerability of intravenous ZD9331 in heavily pretreated patients with ovarian cancer","volume":"91","author":"Rader","year":"2003","journal-title":"Gynecol Oncol"},{"key":"10.1124\/dmd.113.055723_bib137","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1093\/jnci\/85.14.1154","article-title":"Phase I study of (6R)-5,10-dideazatetrahydrofolate: a folate antimetabolite inhibitory to de novo purine synthesis","volume":"85","author":"Ray","year":"1993","journal-title":"J Natl Cancer Inst"},{"key":"10.1124\/dmd.113.055723_bib138","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.1182\/blood.V93.11.3940","article-title":"Expression and functional characterization of the beta-isoform of the folate receptor on CD34(+) cells","volume":"93","author":"Reddy","year":"1999","journal-title":"Blood"},{"key":"10.1124\/dmd.113.055723_bib139","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0026-895X(25)10167-3","article-title":"Biochemical studies on PT523, a potent nonpolyglutamatable antifolate, in cultured cells","volume":"45","author":"Rhee","year":"1994","journal-title":"Mol Pharmacol"},{"issue":"23","key":"10.1124\/dmd.113.055723_bib140","doi-asserted-by":"crossref","first-page":"7947","DOI":"10.1158\/1078-0432.CCR-08-0864","article-title":"Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors","volume":"14","author":"Ricart","year":"2008","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib141","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s002800050017","article-title":"Weekly lometrexol with daily oral folic acid is appropriate for phase II evaluation","volume":"45","author":"Roberts","year":"2000","journal-title":"Cancer Chemother Pharmacol"},{"issue":"18S","key":"10.1124\/dmd.113.055723_bib142","doi-asserted-by":"crossref","first-page":"7142","DOI":"10.1200\/jco.2006.24.18_suppl.7142","article-title":"A phase I study of talotrexin (PT-523) in patients with relapsed or refractory non-small cell lung cancer (NSCLC)","volume":"24","author":"Roca Lima","year":"2006","journal-title":"J Clin Oncol"},{"key":"10.1124\/dmd.113.055723_bib143","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1021\/jm00402a013","article-title":"Methotrexate analogues. 33. N delta-acyl-N alpha-(4-amino-4-deoxypteroyl)-L-ornithine derivatives: synthesis and in vitro antitumor activity","volume":"31","author":"Rosowsky","year":"1988","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib144","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1021\/jm00040a008","article-title":"Synthesis and biological activity of N omega-hemiphthaloyl-alpha,omega- diaminoalkanoic acid analogues of aminopterin and 3\u2032,5-dichloroaminopterin","volume":"37","author":"Rosowsky","year":"1994","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib145","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1002\/1097-0142(19940501)73:9<2432::AID-CNCR2820730929>3.0.CO;2-S","article-title":"Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications","volume":"73","author":"Ross","year":"1994","journal-title":"Cancer"},{"key":"10.1124\/dmd.113.055723_bib146","doi-asserted-by":"crossref","first-page":"10299","DOI":"10.1158\/0008-5472.CAN-10-1873","article-title":"Pemetrexed indirectly activates the metabolic kinase AMPK in human carcinomas","volume":"70","author":"Rothbart","year":"2010","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib147","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1074\/jbc.M309092200","article-title":"Reduced folate carrier gene silencing in multiple antifolate-resistant tumor cell lines is due to a simultaneous loss of function of multiple transcription factors but not promoter methylation","volume":"279","author":"Rothem","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib148","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1074\/jbc.273.5.2526","volume":"273","author":"Roy","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib149","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.addr.2004.01.010","article-title":"Folate receptor endocytosis and trafficking","volume":"56","author":"Sabharanjak","year":"2004","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1124\/dmd.113.055723_bib150","doi-asserted-by":"crossref","first-page":"42105","DOI":"10.1074\/jbc.M206459200","article-title":"Functional role of arginine 373 in substrate translocation by the reduced folate carrier","volume":"277","author":"Sadlish","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib151","first-page":"257","article-title":"The major facilitator superfamily","volume":"1","author":"Saier","year":"1999","journal-title":"J Mol Microbiol Biotechnol"},{"key":"10.1124\/dmd.113.055723_bib152","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s10555-007-9048-0","article-title":"The folate receptor: what does it promise in tissue-targeted therapeutics?","volume":"26","author":"Salazar","year":"2007","journal-title":"Cancer Metastasis Rev"},{"key":"10.1124\/dmd.113.055723_bib153","doi-asserted-by":"crossref","first-page":"4895","DOI":"10.1182\/blood-2010-04-279653","article-title":"A mouse model of hereditary folate malabsorption: deletion of the PCFT gene leads to systemic folate deficiency","volume":"117","author":"Salojin","year":"2011","journal-title":"Blood"},{"key":"10.1124\/dmd.113.055723_bib154","first-page":"551","article-title":"New folate analogs of the 10-deaza-aminopterin series: markedly increased antitumor activity of the 10-ethyl analog compared to the parent compound and methotrexate against some human tumor xenografts in nude mice","volume":"69","author":"Schmid","year":"1985","journal-title":"Cancer Treat Rep"},{"key":"10.1124\/dmd.113.055723_bib155","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1097\/01.COC.0000071944.01707.53","article-title":"ZD9331 as second- or third-line therapy in patients with advanced colorectal cancer: a phase II multicenter trial","volume":"27","author":"Schulz","year":"2004","journal-title":"Am J Clin Oncol"},{"issue":"7","key":"10.1124\/dmd.113.055723_bib156","first-page":"1901","article-title":"A phase I and pharmacokinetic study of 1843U89, a noncompetitive inhibitor of thymidylate synthase, in patients with advanced solid malignancies","volume":"7","author":"Schwartz","year":"2001","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib157","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0083-6729(08)60397-0","article-title":"Folylpolyglutamate synthesis and role in the regulation of one-carbon metabolism","volume":"45","author":"Shane","year":"1989","journal-title":"Vitam Horm"},{"key":"10.1124\/dmd.113.055723_bib158","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/S0026-895X(24)12559-X","article-title":"Mutational analysis of the functional role of conserved arginine and lysine residues in transmembrane domains of the murine reduced folate carrier","volume":"59","author":"Sharina","year":"2001","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib159","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2005.06.025","article-title":"Identification of an intestinal heme transporter","volume":"122","author":"Shayeghi","year":"2005","journal-title":"Cell"},{"key":"10.1124\/dmd.113.055723_bib160","first-page":"1116","article-title":"LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes","volume":"57","author":"Shih","year":"1997","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib161","series-title":"Anticancer Drug Development Guide: Antifolate Drugs in Cancer Therapy","first-page":"183","article-title":"Preclinical Pharmacology Studies and the Clinical Development of a Novel Multitargeted Antifolate, MTA (LY231514)","author":"Shih","year":"1999"},{"key":"10.1124\/dmd.113.055723_bib162","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ymgme.2011.01.008","article-title":"Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption","volume":"103","author":"Shin","year":"2011","journal-title":"Mol Genet Metab"},{"key":"10.1124\/dmd.113.055723_bib163","doi-asserted-by":"crossref","first-page":"5162","DOI":"10.1182\/blood-2010-06-291237","article-title":"Functional roles of aspartate residues of the proton-coupled folate transporter (PCFT-SLC46A1); a D156Y mutation causing hereditary folate malabsorption","volume":"116","author":"Shin","year":"2010","journal-title":"Blood"},{"key":"10.1124\/dmd.113.055723_bib164","doi-asserted-by":"crossref","first-page":"C1159","DOI":"10.1152\/ajpcell.00353.2012","article-title":"Role of the fourth transmembrane domain in proton-coupled folate transporter function as assessed by the substituted cysteine accessibility method","volume":"304","author":"Shin","year":"2013","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1124\/dmd.113.055723_bib165","doi-asserted-by":"crossref","first-page":"C1405","DOI":"10.1152\/ajpcell.00435.2011","article-title":"A P425R mutation of the proton-coupled folate transporter causing hereditary folate malabsorption produces a highly selective alteration in folate binding","volume":"302","author":"Shin","year":"2012","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1124\/dmd.113.055723_bib166","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0006-2952(96)00730-7","article-title":"pH dependence of methotrexate transport by the reduced folate carrier and the folate receptor in L1210 leukemia cells. Further evidence for a third route mediated at low pH","volume":"53","author":"Sierra","year":"1997","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib167","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1016\/0006-2952(79)90599-9","article-title":"Stereospecificity at carbon 6 of fomyltetrahydrofolate as a competitive inhibitor of transport and cytotoxicity of methotrexate in vitro","volume":"28","author":"Sirotnak","year":"1979","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib168","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s002800050823","article-title":"A new analogue of 10-deazaaminopterin with markedly enhanced curative effects against human tumor xenografts in mice","volume":"42","author":"Sirotnak","year":"1998","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib169","first-page":"26","article-title":"New folate analogs of the 10-deaza-aminopterin series. Further evidence for markedly increased antitumor efficacy compared with methotrexate in ascitic and solid murine tumor models","volume":"12","author":"Sirotnak","year":"1984","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib170","doi-asserted-by":"crossref","first-page":"13139","DOI":"10.1016\/S0021-9258(18)90668-X","article-title":"A novel class of genetic variants of the L1210 cell up-regulated for folate analogue transport inward. Isolation, characterization, and degree of metabolic instability of the system","volume":"259","author":"Sirotnak","year":"1984","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib171","first-page":"587","article-title":"Markedly improved efficacy of edatrexate compared to methotrexate in a high-dose regimen with leucovorin rescue against metastatic murine solid tumors","volume":"53","author":"Sirotnak","year":"1993","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib172","first-page":"6117","article-title":"Enhanced antitumor activity for the thymidylate synthase inhibitor 1843U89 through decreased host toxicity with oral folic acid","volume":"55","author":"Smith","year":"1995","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib173","series-title":"Anticancer Drug Development Guide: Antifolate Drugs in Cancer Therapy","first-page":"59","article-title":"A Potent, Noncopetitive Thymidylate Synthase Inhibitor-Preclinical and Preliminary Clinical Studies","author":"Smith","year":"1999"},{"key":"10.1124\/dmd.113.055723_bib174","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/S0959-8049(03)00271-5","article-title":"A phase II\/III study comparing intravenous ZD9331 with gemcitabine in patients with pancreatic cancer","volume":"39","author":"Smith","year":"2003","journal-title":"Eur J Cancer"},{"key":"10.1124\/dmd.113.055723_bib175","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1126\/science.1167256","article-title":"Folate transport by the choroid plexus in vitro","volume":"187","author":"Spector","year":"1975","journal-title":"Science"},{"key":"10.1124\/dmd.113.055723_bib176","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bbrc.2009.07.116","article-title":"Functional elements in the minimal promoter of the human proton-coupled folate transporter","volume":"388","author":"Stark","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1124\/dmd.113.055723_bib177","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.ajhg.2009.08.005","article-title":"Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism","volume":"85","author":"Steinfeld","year":"2009","journal-title":"Am J Hum Genet"},{"key":"10.1124\/dmd.113.055723_bib178","series-title":"Historical Perspective on Key Advances in the Biochemistry and Physiology of Folates","author":"Stokstad","year":"1990"},{"key":"10.1124\/dmd.113.055723_bib179","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/jcp.10324","article-title":"Folate uptake in the human intestine: promoter activity and effect of folate deficiency","volume":"196","author":"Subramanian","year":"2003","journal-title":"J Cell Physiol"},{"key":"10.1124\/dmd.113.055723_bib180","doi-asserted-by":"crossref","first-page":"C233","DOI":"10.1152\/ajpcell.00468.2007","article-title":"Apical membrane targeting and trafficking of the human proton-coupled transporter in polarized epithelia","volume":"294","author":"Subramanian","year":"2008","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1124\/dmd.113.055723_bib181","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1586\/era.11.136","article-title":"Raltitrexed in mesothelioma","volume":"11","author":"Surmont","year":"2011","journal-title":"Expert Rev Anticancer Ther"},{"key":"10.1124\/dmd.113.055723_bib182","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1021\/jm00145a012","article-title":"Synthesis of the antileukemic agents 5,10-dideazaaminopterin and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin","volume":"28","author":"Taylor","year":"1985","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib183","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.1021\/jm00101a023","article-title":"A dideazatetrahydrofolate analogue lacking a chiral center at C-6, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid, is an inhibitor of thymidylate synthase","volume":"35","author":"Taylor","year":"1992","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib184","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.2146\/news090080","article-title":"FDA approves pralatrexate for treatment of rare lymphoma","volume":"66","author":"Thompson","year":"2009","journal-title":"Am J Health Syst Pharm"},{"key":"10.1124\/dmd.113.055723_bib185","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev.nutr.012809.104810","article-title":"Compartmentalization of Mammalian folate-mediated one-carbon metabolism","volume":"30","author":"Tibbetts","year":"2010","journal-title":"Annu Rev Nutr"},{"key":"10.1124\/dmd.113.055723_bib186","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/0006-2952(91)90283-B","article-title":"Compartmentation of intracellular folates. Failure to interconvert tetrahydrofolate cofactors to dihydrofolate in mitochondria of L1210 leukemia cells treated with trimetrexate","volume":"42","author":"Trent","year":"1991","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib187","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.1016\/S0021-9258(19)67615-5","article-title":"Rate and extent of interconversion of tetrahydrofolate cofactors to dihydrofolate after cessation of dihydrofolate reductase activity in stationary versus log phase L1210 leukemia cells","volume":"266","author":"Trent","year":"1991","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib188","doi-asserted-by":"crossref","first-page":"5299","DOI":"10.1167\/iovs.07-0288","article-title":"Cloning and functional characterization of the proton-coupled electrogenic folate transporter and analysis of its expression in retinal cell types","volume":"48","author":"Umapathy","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1124\/dmd.113.055723_bib189","doi-asserted-by":"crossref","first-page":"17846","DOI":"10.1074\/jbc.M109.008060","article-title":"The functional roles of the His247 and His281 residues in folate and proton translocation mediated by the human proton-coupled folate transporter SLC46A1","volume":"284","author":"Unal","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib190","doi-asserted-by":"crossref","first-page":"C66","DOI":"10.1152\/ajpcell.00096.2009","article-title":"Role of the glutamate 185 residue in proton translocation mediated by the proton-coupled folate transporter SLC46A1","volume":"297","author":"Unal","year":"2009","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1124\/dmd.113.055723_bib191","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/j.bbamem.2008.03.009","article-title":"N-linked glycosylation and its impact on the electrophoretic mobility and function of the human proton-coupled folate transporter (HsPCFT)","volume":"1778","author":"Unal","year":"2008","journal-title":"Biochim Biophys Acta"},{"key":"10.1124\/dmd.113.055723_bib192","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00280-013-2231-9","article-title":"The membrane transport and polyglutamation of pralatrexate: a new-generation dihydrofolate reductase inhibitor","volume":"72","author":"Visentin","year":"2013","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib193","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.hoc.2012.02.002","article-title":"The antifolates","volume":"26","author":"Visentin","year":"2012","journal-title":"Hematol Oncol Clin North Am"},{"key":"10.1124\/dmd.113.055723_bib194","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1124\/mol.112.078642","article-title":"Augmentation of reduced folate carrier-mediated folate\/antifolate transport through an antiport mechanism with 5-aminoimidazole-4-carboxamide riboside monophosphate","volume":"82","author":"Visentin","year":"2012","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib195","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1021\/jm9015729","volume":"53","author":"Wang","year":"2010","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib196","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1021\/jm201688n","volume":"55","author":"Wang","year":"2012","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib197","doi-asserted-by":"crossref","first-page":"7150","DOI":"10.1021\/jm200739e","volume":"54","author":"Wang","year":"2011","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib198","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0005-2736(01)00340-6","article-title":"Localization of the murine reduced folate carrier as assessed by immunohistochemical analysis","volume":"1513","author":"Wang","year":"2001","journal-title":"Biochim Biophys Acta"},{"key":"10.1124\/dmd.113.055723_bib199","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nrc3110","article-title":"Dysregulated pH: a perfect storm for cancer progression","volume":"11","author":"Webb","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"10.1124\/dmd.113.055723_bib200","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/rheumatology\/kem279","article-title":"Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis","volume":"47","author":"Wessels","year":"2008","journal-title":"Rheumatology (Oxford)"},{"key":"10.1124\/dmd.113.055723_bib201","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S0026-895X(25)10494-X","article-title":"Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: correlates of molecular-structure and biological activity","volume":"48","author":"Westerhof","year":"1995","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib202","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1042\/bj20020512","article-title":"The human reduced folate carrier gene is ubiquitously and differentially expressed in normal human tissues: identification of seven non-coding exons and characterization of a novel promoter","volume":"367","author":"Whetstine","year":"2002","journal-title":"Biochem J"},{"issue":"11","key":"10.1124\/dmd.113.055723_bib203","first-page":"3416","article-title":"Single nucleotide polymorphisms in the human reduced folate carrier: characterization of a high-frequency G\/A variant at position 80 and transport properties of the His(27) and Arg(27) carriers","volume":"7","author":"Whetstine","year":"2001","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib204","doi-asserted-by":"crossref","first-page":"43873","DOI":"10.1074\/jbc.M208296200","article-title":"The human reduced folate carrier gene is regulated by the AP2 and sp1 transcription factor families and a functional 61-base pair polymorphism","volume":"277","author":"Whetstine","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib205","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0021-9258(17)38295-9","article-title":"Lack of stereospecificity at carbon 6 of methyltetrahydrofolate transport in Ehrlich ascites tumor cells. Carrier-mediated transport of both stereoisomers","volume":"253","author":"White","year":"1978","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib206","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1074\/jbc.270.7.2987","article-title":"Isolation of a human cDNA that complements a mutant hamster cell defective in methotrexate uptake","volume":"270","author":"Williams","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib207","doi-asserted-by":"crossref","first-page":"5810","DOI":"10.1016\/S0021-9258(17)37534-8","article-title":"Isolation of a hamster cDNA clone coding for a function involved in methotrexate uptake","volume":"269","author":"Williams","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib208","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1517\/17425250903307455","article-title":"Raltitrexed: optimism and reality","volume":"5","author":"Wilson","year":"2009","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"10.1124\/dmd.113.055723_bib209","doi-asserted-by":"crossref","first-page":"46755","DOI":"10.1074\/jbc.M408696200","article-title":"Restoration of transport activity by co-expression of human reduced folate carrier half-molecules in transport-impaired K562 cells: localization of a substrate binding domain to transmembrane domains 7-12","volume":"279","author":"Witt","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib210","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1111\/j.1471-4159.2007.05095.x","article-title":"Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model","volume":"104","author":"Wollack","year":"2008","journal-title":"J Neurochem"},{"key":"10.1124\/dmd.113.055723_bib211","doi-asserted-by":"crossref","first-page":"17468","DOI":"10.1074\/jbc.270.29.17468","article-title":"Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells","volume":"270","author":"Wong","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib212","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/S0005-2736(98)00118-7","article-title":"Effects of the loss of capacity for N-glycosylation on the transport activity and cellular localization of the human reduced folate carrier","volume":"1375","author":"Wong","year":"1998","journal-title":"Biochim Biophys Acta"},{"key":"10.1124\/dmd.113.055723_bib213","doi-asserted-by":"crossref","first-page":"10388","DOI":"10.1074\/jbc.274.15.10388","article-title":"Impaired membrane transport in methotrexate-resistant CCRF-CEM cells involves early translation termination and increased turnover of a mutant reduced folate carrier","volume":"274","author":"Wong","year":"1999","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib214","doi-asserted-by":"crossref","first-page":"39990","DOI":"10.1074\/jbc.M103181200","article-title":"Methylation-dependent silencing of the reduced folate carrier gene in inherently methotrexate-resistant human breast cancer cells","volume":"276","author":"Worm","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib215","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0006-2952(00)00294-X","article-title":"Efficient utilization of the reduced folate carrier in CCRF-CEM human leukemic lymphoblasts by the potent antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L- ornithine (PT523) and its B-ring analogues","volume":"60","author":"Wright","year":"2000","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib216","doi-asserted-by":"crossref","first-page":"6811","DOI":"10.1021\/jm100509v","article-title":"Folate-targeted therapies for cancer","volume":"53","author":"Xia","year":"2010","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.113.055723_bib217","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/978-94-007-2199-9_9","article-title":"Folate-linked drugs for the treatment of cancer and inflammatory diseases","volume":"56","author":"Yang","year":"2012","journal-title":"Subcell Biochem"},{"key":"10.1124\/dmd.113.055723_bib218","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1113\/jphysiol.1995.sp020558","article-title":"Mammalian Na+\/H+ exchanger gene family: structure and function studies","volume":"269","author":"Yun","year":"1995","journal-title":"Am J Physiol"},{"key":"10.1124\/dmd.113.055723_bib219","doi-asserted-by":"crossref","first-page":"19065","DOI":"10.1074\/jbc.273.30.19065","article-title":"A mutated murine reduced folate carrier (RFC1) with increased affinity for folic acid, decreased affinity for methotrexate, and an obligatory anion requirement for transport function","volume":"273","author":"Zhao","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib220","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev-nutr-072610-145133","article-title":"Mechanisms of membrane transport of folates into cells and across epithelia","volume":"31","author":"Zhao","year":"2011","journal-title":"Annu Rev Nutr"},{"issue":"8","key":"10.1124\/dmd.113.055723_bib221","first-page":"3304","article-title":"Sensitivity to 5,10-dideazatetrahydrofolate is fully conserved in a murine leukemia cell line highly resistant to methotrexate due to impaired transport mediated by the reduced folate carrier","volume":"6","author":"Zhao","year":"2000","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib222","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/S0006-2952(99)00257-9","article-title":"Discrimination among reduced folates and methotrexate as transport substrates by a phenylalanine substitution for serine within the predicted eighth transmembrane domain of the reduced folate carrier","volume":"58","author":"Zhao","year":"1999","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib223","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0006-2952(01)00532-9","article-title":"Marked suppression of the activity of some, but not all, antifolate compounds by augmentation of folate cofactor pools within tumor cells","volume":"61","author":"Zhao","year":"2001","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib224","doi-asserted-by":"crossref","first-page":"C1512","DOI":"10.1152\/ajpcell.00547.2001","article-title":"Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells","volume":"282","author":"Zhao","year":"2002","journal-title":"Am J Physiol Cell Physiol"},{"issue":"2","key":"10.1124\/dmd.113.055723_bib225","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1158\/1078-0432.CCR-1066-03","article-title":"A prominent low-pH methotrexate transport activity in human solid tumors: contribution to the preservation of methotrexate pharmacologic activity in HeLa cells lacking the reduced folate carrier","volume":"10","author":"Zhao","year":"2004","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib226","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1074\/jbc.M007919200","article-title":"Impact of the reduced folate carrier on the accumulation of active thiamin metabolites in murine leukemia cells","volume":"276","author":"Zhao","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib227","doi-asserted-by":"crossref","first-page":"7431","DOI":"10.1038\/sj.onc.1206946","article-title":"Resistance to antifolates","volume":"22","author":"Zhao","year":"2003","journal-title":"Oncogene"},{"key":"10.1124\/dmd.113.055723_bib228","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s10555-007-9047-1","article-title":"The molecular identity and characterization of a Proton-coupled Folate Transporter\u2014PCFT; biological ramifications and impact on the activity of pemetrexed","volume":"26","author":"Zhao","year":"2007","journal-title":"Cancer Metastasis Rev"},{"key":"10.1124\/dmd.113.055723_bib229","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.mam.2012.07.006","article-title":"Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors","volume":"34","author":"Zhao","year":"2013","journal-title":"Mol Aspects Med"},{"key":"10.1124\/dmd.113.055723_bib230","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1158\/0008-5472.CAN-03-3953","article-title":"Selective preservation of pemetrexed pharmacological activity in HeLa cells lacking the reduced folate carrier: association with the presence of a secondary transport pathway","volume":"64","author":"Zhao","year":"2004","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.113.055723_bib231","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1017\/S1462399409000969","article-title":"Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues","volume":"11","author":"Zhao","year":"2009","journal-title":"Expert Rev Mol Med"},{"key":"10.1124\/dmd.113.055723_bib232","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1182\/blood-2007-02-077099","article-title":"The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption","volume":"110","author":"Zhao","year":"2007","journal-title":"Blood"},{"key":"10.1124\/dmd.113.055723_bib233","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1074\/jbc.M807665200","article-title":"A role for the proton-coupled folate transporter (PCFT-SLC46A1) in folate receptor-mediated endocytosis","volume":"284","author":"Zhao","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib234","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1124\/mol.108.045443","article-title":"The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier","volume":"74","author":"Zhao","year":"2008","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib235","doi-asserted-by":"crossref","first-page":"10224","DOI":"10.1074\/jbc.C000905200","article-title":"Rescue of embryonic lethality in reduced folate carrier-deficient mice by maternal folic acid supplementation reveals early neonatal failure of hematopoietic organs","volume":"276","author":"Zhao","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib236","doi-asserted-by":"crossref","first-page":"24150","DOI":"10.1074\/jbc.M111.236539","article-title":"Random mutagenesis of the proton-coupled folate transporter (SLC46A1), clustering of mutations, and the bases for associated losses of function","volume":"286","author":"Zhao","year":"2011","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.113.055723_bib237","doi-asserted-by":"crossref","first-page":"C673","DOI":"10.1152\/ajpcell.00123.2012","article-title":"Identification of a functionally critical GXXG motif and its relationship to the folate binding site of the proton-coupled folate transporter (PCFT-SLC46A1)","volume":"303","author":"Zhao","year":"2012","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1124\/dmd.113.055723_bib238","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1021\/bi9021439","article-title":"Membrane topological analysis of the proton-coupled folate transporter (PCFT-SLC46A1) by the substituted cysteine accessibility method","volume":"49","author":"Zhao","year":"2010","journal-title":"Biochemistry"},{"key":"10.1124\/dmd.113.055723_bib239","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1124\/mol.113.085605","article-title":"Inhibition of the proton-coupled folate transporter (PCFT-SLC46A1) by bicarbonate and other anions","volume":"84","author":"Zhao","year":"2013","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.113.055723_bib240","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0005-2736(03)00136-6","article-title":"Residues 45 and 404 in the murine reduced folate carrier may interact to alter carrier binding and mobility","volume":"1613","author":"Zhao","year":"2003","journal-title":"Biochim Biophys Acta"}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624113864?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624113864?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/dmd.113.055723","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T19:34:45Z","timestamp":1739907285000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955624113864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4]]},"references-count":240,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["S0090955624113864"],"URL":"https:\/\/doi.org\/10.1124\/dmd.113.055723","relation":{},"ISSN":["0090-9556"],"issn-type":[{"value":"0090-9556","type":"print"}],"subject":[],"published":{"date-parts":[[2014,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The Major Facilitative Folate Transporters Solute Carrier 19A1 and Solute Carrier 46A1: Biology and Role in Antifolate Chemotherapy of Cancer","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/dmd.113.055723","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2014 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}