PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 28939533-3 2017 This requires considering a set of experimentally validated protein targets in the folate pathway of major pathogenic trypanosomatid parasites and humans: (i) the primary parasite on-targets: pteridine reductase 1 (PTR1) (absent in humans) and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), (ii) the primary off-targets: human DHFR and TS, and (iii) the secondary on-target: human folate receptor beta, a folate/antifolate transporter. Folic Acid 83-89 dihydrofolate reductase Homo sapiens 303-307 30120883-3 2018 This study aims to evaluate the association between genetic defects in folate metabolism pathway genes, mainly: Folate hydrolase 1 (FOLH1), Dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate reductase (MTHFR) and neural tube defects from eastern India. Folic Acid 71-77 dihydrofolate reductase Homo sapiens 140-163 30120883-3 2018 This study aims to evaluate the association between genetic defects in folate metabolism pathway genes, mainly: Folate hydrolase 1 (FOLH1), Dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate reductase (MTHFR) and neural tube defects from eastern India. Folic Acid 71-77 dihydrofolate reductase Homo sapiens 165-169 29321536-5 2018 Our results revealed that these genes could be novel and more promising anticancer targets than dihydrofolate reductase (DHFR), the current target of drug therapy linked with folate metabolism, suggesting the rationale of drug discovery in cancer medicine. Folic Acid 103-109 dihydrofolate reductase Homo sapiens 121-125 28939533-3 2017 This requires considering a set of experimentally validated protein targets in the folate pathway of major pathogenic trypanosomatid parasites and humans: (i) the primary parasite on-targets: pteridine reductase 1 (PTR1) (absent in humans) and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), (ii) the primary off-targets: human DHFR and TS, and (iii) the secondary on-target: human folate receptor beta, a folate/antifolate transporter. Folic Acid 83-89 dihydrofolate reductase Homo sapiens 349-353 28939595-3 2017 This work presents a complete study of a plant DHFR-TS (dihydrofolate reductase-thymidylate synthase) gene family that implements the penultimate step in folate biosynthesis. Folic Acid 63-69 dihydrofolate reductase Homo sapiens 47-51 28939595-4 2017 We demonstrate that one of the DHFR-TS isoforms (DHFR-TS3) operates as an inhibitor of its two homologs, thus regulating DHFR and TS activities and, as a consequence, folate abundance. Folic Acid 167-173 dihydrofolate reductase Homo sapiens 31-35 28939595-4 2017 We demonstrate that one of the DHFR-TS isoforms (DHFR-TS3) operates as an inhibitor of its two homologs, thus regulating DHFR and TS activities and, as a consequence, folate abundance. Folic Acid 167-173 dihydrofolate reductase Homo sapiens 49-53 28939595-4 2017 We demonstrate that one of the DHFR-TS isoforms (DHFR-TS3) operates as an inhibitor of its two homologs, thus regulating DHFR and TS activities and, as a consequence, folate abundance. Folic Acid 167-173 dihydrofolate reductase Homo sapiens 49-53 28188287-1 2017 Dihydrofolate reductase (DHFR) plays a key role in folate metabolism and is a target molecule of methotrexate. Folic Acid 7-13 dihydrofolate reductase Homo sapiens 25-29 28496133-3 2017 Dihydrofolate reductase (DHFR) is a key enzyme to regulate folate metabolism, however folate/DHFR activity in oligodendrocyte development has not been fully understood. Folic Acid 7-13 dihydrofolate reductase Homo sapiens 25-29 28496133-3 2017 Dihydrofolate reductase (DHFR) is a key enzyme to regulate folate metabolism, however folate/DHFR activity in oligodendrocyte development has not been fully understood. Folic Acid 7-13 dihydrofolate reductase Homo sapiens 93-97 28496133-4 2017 Here we show that folate enhances oligodendrocyte maturation both in vitro and in vivo, which is accompanied with upregulation of oligodendrocyte-specific DHFR expression. Folic Acid 18-24 dihydrofolate reductase Homo sapiens 155-159 28496133-5 2017 On the other hand, pharmacological inhibition of DHFR by methotrexate (MTX) causes severe defects in oligodendrocyte survival and differentiation, which could be reversed by folate intake. Folic Acid 174-180 dihydrofolate reductase Homo sapiens 49-53 28338744-1 2017 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 96-102 dihydrofolate reductase Homo sapiens 114-118 28338744-1 2017 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 133-139 dihydrofolate reductase Homo sapiens 89-112 28338744-1 2017 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 133-139 dihydrofolate reductase Homo sapiens 114-118 27013776-3 2016 To be used, folic acid must be converted to 7,8-dihydrofolate by dihydrofolate reductase to generate one-carbon derivatives serving as important cellular cofactors in the synthesis of nucleotides and amino acids required for cell growth. Folic Acid 12-22 dihydrofolate reductase Homo sapiens 65-88 27919952-3 2016 The mRNA expression levels of Alimta -target enzymes [thymidylate synthase (TYMS); dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT)], Alimta -metabolizing enzymes [gamma-glutamyl hydrase (GGH) and folylpolyglutamate synthase] and an Alimta transporter [reduce folate carrier (RFC)] were measured and examined for potential correlations to chemosensitivity. Folic Acid 90-96 dihydrofolate reductase Homo sapiens 108-112 27994750-1 2016 Current treatment of toxoplasmosis targets the parasite"s folate metabolism through inhibition of dihydrofolate reductase (DHFR). Folic Acid 58-64 dihydrofolate reductase Homo sapiens 123-127 27131640-9 2016 In a recent study we found that the risk for unilateral retinoblastoma in offspring is 4 fold higher in women that are homozygotes for the 19 bp deletion in the DHFR gene and took folic acid supplement during pregnancy. Folic Acid 180-190 dihydrofolate reductase Homo sapiens 161-165 27189223-3 2016 Here, folic acid, a ligand of dihydrofolate reductase (DHFR), was hyperpolarized on (1)H spins using dissolution dynamic nuclear polarization (D-DNP). Folic Acid 6-16 dihydrofolate reductase Homo sapiens 30-53 27189223-3 2016 Here, folic acid, a ligand of dihydrofolate reductase (DHFR), was hyperpolarized on (1)H spins using dissolution dynamic nuclear polarization (D-DNP). Folic Acid 6-16 dihydrofolate reductase Homo sapiens 55-59 26229988-2 2016 In this assay, free methotrexate and folic acid Au nanoparticles competed for human dihydrofolate reductase (hDHFR)-functionalized Au nanoparticles (Au NP). Folic Acid 37-47 dihydrofolate reductase Homo sapiens 109-114 26929741-1 2016 BACKGROUND: Methotrexate is an important chemotherapeutic drug widely known as an inhibitor of dihydrofolate reductase (DHFR) which inhibits the reduction of folic acid. Folic Acid 158-168 dihydrofolate reductase Homo sapiens 120-124 26229988-2 2016 In this assay, free methotrexate and folic acid Au nanoparticles competed for human dihydrofolate reductase (hDHFR)-functionalized Au nanoparticles (Au NP). Folic Acid 37-47 dihydrofolate reductase Homo sapiens 84-107 26929741-1 2016 BACKGROUND: Methotrexate is an important chemotherapeutic drug widely known as an inhibitor of dihydrofolate reductase (DHFR) which inhibits the reduction of folic acid. Folic Acid 158-168 dihydrofolate reductase Homo sapiens 95-118 26414244-8 2015 Application of folic acid (FA) restored DHFR levels, NO bioavailability, and BH4 levels under hypoxia. Folic Acid 15-25 dihydrofolate reductase Homo sapiens 40-44 26881719-6 2016 DHFR, an enzyme of the folate biosynthesis pathway is an established chemotherapeutic target, initially explored for anti-cancer drug discovery. Folic Acid 23-29 dihydrofolate reductase Homo sapiens 0-4 27213086-1 2016 Structural basis for exploration into MDM2 and MDM2-DHFR interaction plays a vital role in analyzing the obstruction in folate metabolism, nonsynthesis of purines, and further epigenetic regulation in Homo sapiens. Folic Acid 120-126 dihydrofolate reductase Homo sapiens 52-56 27064332-0 2016 Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine. Folic Acid 14-24 dihydrofolate reductase Homo sapiens 114-137 25441416-2 2015 MTX concentrations in a patient"s serum undergoing chemotherapy treatments can be determined by surface plasmon resonance (SPR) sensing using folic acid-functionalized gold nanoparticles (FA-AuNP) in competition with MTX for the bioreceptor, human dihydrofolate reductase (hDHFR) immobilized on the SPR sensor chip. Folic Acid 142-152 dihydrofolate reductase Homo sapiens 273-278 26354538-2 2015 In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. Folic Acid 69-75 dihydrofolate reductase Homo sapiens 199-222 26354538-2 2015 In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. Folic Acid 69-75 dihydrofolate reductase Homo sapiens 224-228 26354538-2 2015 In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. Folic Acid 136-142 dihydrofolate reductase Homo sapiens 199-222 26354538-2 2015 In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. Folic Acid 136-142 dihydrofolate reductase Homo sapiens 224-228 26022931-4 2015 Dihydrofolate reductase (DHFR) plays a critical role in regulating the metabolism of folate. Folic Acid 7-13 dihydrofolate reductase Homo sapiens 25-29 26269242-1 2015 BACKGROUND: Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism. Folic Acid 78-88 dihydrofolate reductase Homo sapiens 12-35 26269242-1 2015 BACKGROUND: Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism. Folic Acid 78-88 dihydrofolate reductase Homo sapiens 37-41 26269242-1 2015 BACKGROUND: Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism. Folic Acid 19-25 dihydrofolate reductase Homo sapiens 37-41 26144049-3 2015 The present study reveals that pharmacological and antisense oligonucleotide mediated inhibition of DHFR, an integral enzyme in the folate pathway, results in specific changes in the size and shape of the midface and embryonic mouth. Folic Acid 132-138 dihydrofolate reductase Homo sapiens 100-104 26131691-14 2015 In this low-dose regime, folate supplements are given to mitigate side effects by bypassing the biochemical requirement for DHFR. Folic Acid 25-31 dihydrofolate reductase Homo sapiens 124-128 25315410-2 2015 Sulfonamide antibiotics block synthesis of folic acid by inhibiting dihydrofolate reductase (DHFR) while TCS block fatty acid synthesis through inhibition of enoyl-ACP reductase (FabI). Folic Acid 43-53 dihydrofolate reductase Homo sapiens 68-91 25315410-2 2015 Sulfonamide antibiotics block synthesis of folic acid by inhibiting dihydrofolate reductase (DHFR) while TCS block fatty acid synthesis through inhibition of enoyl-ACP reductase (FabI). Folic Acid 43-53 dihydrofolate reductase Homo sapiens 93-97 24739308-6 2014 Here, we report the epistatic interaction between dhfr mutations and amplification of the gene encoding the first upstream enzyme in the folate pathway, GTP cyclohydrolase I (GCH1). Folic Acid 137-143 dihydrofolate reductase Homo sapiens 50-54 26875486-3 2015 Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. Folic Acid 75-81 dihydrofolate reductase Homo sapiens 40-44 26875486-2 2015 Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Folic Acid 74-84 dihydrofolate reductase Homo sapiens 0-23 26875486-2 2015 Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Folic Acid 74-84 dihydrofolate reductase Homo sapiens 25-29 26875486-2 2015 Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Folic Acid 111-117 dihydrofolate reductase Homo sapiens 0-23 26875486-2 2015 Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Folic Acid 111-117 dihydrofolate reductase Homo sapiens 25-29 23973753-1 2013 Folic acid (FA), also named vitamin B9, is an essential cofactor for the synthesis of DNA bases and other biomolecules after bioactivation by dihydrofolate reductase (DHFR). Folic Acid 0-10 dihydrofolate reductase Homo sapiens 142-165 27025730-3 2014 The folate metabolic pathway leads to synthesis of required precursors for cellular function and contains a critical node, dihydrofolate reductase (DHFR), which is shared between prokaryotes and eukaryotes. Folic Acid 4-10 dihydrofolate reductase Homo sapiens 123-146 27025730-3 2014 The folate metabolic pathway leads to synthesis of required precursors for cellular function and contains a critical node, dihydrofolate reductase (DHFR), which is shared between prokaryotes and eukaryotes. Folic Acid 4-10 dihydrofolate reductase Homo sapiens 148-152 24705454-1 2014 We report that a shorter Debye length and, as a consequence, decreased colloidal stability are required for the molecular interaction of folic acid-modified Au nanoparticles (Au NPs) to occur on a surface-bound receptor, human dihydrofolate reductase (hDHFR). Folic Acid 137-147 dihydrofolate reductase Homo sapiens 227-250 24705454-1 2014 We report that a shorter Debye length and, as a consequence, decreased colloidal stability are required for the molecular interaction of folic acid-modified Au nanoparticles (Au NPs) to occur on a surface-bound receptor, human dihydrofolate reductase (hDHFR). Folic Acid 137-147 dihydrofolate reductase Homo sapiens 252-257 24705454-4 2014 Longer Debye lengths led to poorer SPR responses, revealing a reduced affinity of the folic acid-modified Au NPs for hDHFR. Folic Acid 86-96 dihydrofolate reductase Homo sapiens 117-122 27025730-10 2014 These inhibitors are also likely to interact with the enzymatic neighbors in the folate pathway that bind products of the DHFR or DHPS enzymes and/or substrates of similar substructure. Folic Acid 81-87 dihydrofolate reductase Homo sapiens 122-126 23973753-1 2013 Folic acid (FA), also named vitamin B9, is an essential cofactor for the synthesis of DNA bases and other biomolecules after bioactivation by dihydrofolate reductase (DHFR). Folic Acid 0-10 dihydrofolate reductase Homo sapiens 167-171 23973753-1 2013 Folic acid (FA), also named vitamin B9, is an essential cofactor for the synthesis of DNA bases and other biomolecules after bioactivation by dihydrofolate reductase (DHFR). Folic Acid 28-38 dihydrofolate reductase Homo sapiens 142-165 23973753-1 2013 Folic acid (FA), also named vitamin B9, is an essential cofactor for the synthesis of DNA bases and other biomolecules after bioactivation by dihydrofolate reductase (DHFR). Folic Acid 28-38 dihydrofolate reductase Homo sapiens 167-171 23707606-13 2013 Activity assays verified that human DHFR has very low affinity for 7,8-BH2 (DHF<Km>7,8-BH2) and folic acid inhibits 7,8-BH2 recycling. Folic Acid 102-112 dihydrofolate reductase Homo sapiens 36-40 24053355-1 2013 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 96-102 dihydrofolate reductase Homo sapiens 114-118 24053355-1 2013 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 133-139 dihydrofolate reductase Homo sapiens 89-112 24053355-1 2013 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 133-139 dihydrofolate reductase Homo sapiens 114-118 23707606-14 2013 We conclude that low activity of endothelial DHFR is an important factor limiting the benefits of BH4 therapies, which may be further aggravated by folate supplements. Folic Acid 148-154 dihydrofolate reductase Homo sapiens 45-49 23421317-0 2013 DHFR 19-bp deletion and SHMT C1420T polymorphisms and metabolite concentrations of the folate pathway in individuals with Down syndrome. Folic Acid 87-93 dihydrofolate reductase Homo sapiens 0-4 23552564-6 2013 The effects of 2 of these compounds were mostly reversed by folic acid, validating DHFR inhibitory activity. Folic Acid 60-70 dihydrofolate reductase Homo sapiens 83-87 23799623-10 2013 Exogenously added folic acid reversed the MTX-mediated DHFR inhibition following either MTX or MTX + ASA treatments. Folic Acid 18-28 dihydrofolate reductase Homo sapiens 55-59 23421317-3 2013 AIM: Investigate the association between Dihydrofolate reductase (DHFR) 19-base pair (bp) deletion and Serine hydroxymethyltransferase (SHMT) C1420T polymorphisms and serum folate and plasma Hcy and methylmalonic acid (MMA) concentrations in 85 individuals with DS. Folic Acid 48-54 dihydrofolate reductase Homo sapiens 66-70 23421317-6 2013 RESULTS: Individuals with DHFR DD/SHMT TT genotypes presented increased folate concentrations (p=0.004) and the DHFR II/SHMT TT genotypes were associated with increased MMA concentrations (p=0.008). Folic Acid 72-78 dihydrofolate reductase Homo sapiens 26-30 23421317-8 2013 CONCLUSION: There is an association between DHFR DD/SHMT TT and DHFR II/SHMT TT combined genotypes and folate and MMA concentrations in individuals with DS. Folic Acid 103-109 dihydrofolate reductase Homo sapiens 44-48 23421317-8 2013 CONCLUSION: There is an association between DHFR DD/SHMT TT and DHFR II/SHMT TT combined genotypes and folate and MMA concentrations in individuals with DS. Folic Acid 103-109 dihydrofolate reductase Homo sapiens 64-68 22648968-7 2012 In a subgroup of 167 mothers with data on prenatal intake of supplements containing folic acid (a synthetic form of folate), DHFR19bpdel-associated risk was elevated significantly only among those who reported taking folic acid supplements. Folic Acid 84-94 dihydrofolate reductase Homo sapiens 125-129 22648968-7 2012 In a subgroup of 167 mothers with data on prenatal intake of supplements containing folic acid (a synthetic form of folate), DHFR19bpdel-associated risk was elevated significantly only among those who reported taking folic acid supplements. Folic Acid 116-122 dihydrofolate reductase Homo sapiens 125-129 22648968-7 2012 In a subgroup of 167 mothers with data on prenatal intake of supplements containing folic acid (a synthetic form of folate), DHFR19bpdel-associated risk was elevated significantly only among those who reported taking folic acid supplements. Folic Acid 217-227 dihydrofolate reductase Homo sapiens 125-129 22648968-9 2012 CONCLUSIONS: Maternal homozygosity for a polymorphism in the DHFR gene necessary for converting synthetic folic acid into biologic folate was associated with an increased risk for retinoblastoma. Folic Acid 106-116 dihydrofolate reductase Homo sapiens 61-65 22648968-9 2012 CONCLUSIONS: Maternal homozygosity for a polymorphism in the DHFR gene necessary for converting synthetic folic acid into biologic folate was associated with an increased risk for retinoblastoma. Folic Acid 131-137 dihydrofolate reductase Homo sapiens 61-65 22571483-3 2012 MTX, the monoglutamate form (MTXG1) inhibits the dihydrofolate reductase (DHFR) implicated in the folate cycle. Folic Acid 56-62 dihydrofolate reductase Homo sapiens 74-78 22943049-1 2012 A competitive binding assay based on localized surface plasmon resonance (LSPR) of folic acid-functionalized gold nanoparticles (FA-AuNPs) and human dihydrofolate reductase enzyme (hDHFR) was developed to detect nanomolar to micromolar concentrations of the widely applied anti-cancer drug, methotrexate (MTX). Folic Acid 83-93 dihydrofolate reductase Homo sapiens 181-186 22530664-2 2012 MTX is a folate analog that inhibits dihydrofolate reductase, thereby blocking de novo purine synthesis. Folic Acid 9-15 dihydrofolate reductase Homo sapiens 37-60 21956523-4 2012 PDX was developed as a synthetic folate analog antimetabolite that competitively inhibits dihydrofolate reductase (DHFR). Folic Acid 33-39 dihydrofolate reductase Homo sapiens 90-113 21956523-4 2012 PDX was developed as a synthetic folate analog antimetabolite that competitively inhibits dihydrofolate reductase (DHFR). Folic Acid 33-39 dihydrofolate reductase Homo sapiens 115-119 21126022-1 2011 Folate analogue inhibitors of Leishmania major pteridine reductase (PTR1) are potential antiparasitic drug candidates for combined therapy with dihydrofolate reductase (DHFR) inhibitors. Folic Acid 0-6 dihydrofolate reductase Homo sapiens 169-173 21876184-1 2011 Human dihydrofolate reductase (DHFR) was previously thought to be the only enzyme capable of the reduction of dihydrofolate to tetrahydrofolate; an essential reaction necessary to ensure a continuous supply of biologically active folate. Folic Acid 13-19 dihydrofolate reductase Homo sapiens 31-35 21310276-1 2011 Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. Folic Acid 7-13 dihydrofolate reductase Homo sapiens 25-29 21310277-11 2011 DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate. Folic Acid 57-63 dihydrofolate reductase Homo sapiens 0-4 21726415-7 2011 Loop residues 58-66 in CgDHFR and human DHFR are 1 and 3 A closer to the folate binding site, respectively, than loop residues in CaDHFR, suggesting that a properly size ligand could be a potent and selective dual inhibitor of CaDHFR and CgDHFR. Folic Acid 73-79 dihydrofolate reductase Homo sapiens 25-29 21568878-1 2011 A set of hydroxamate derivatives of folic acid and methotrexate (MTX) was synthesized and evaluated for the inhibitory activity against histone deacetylase (HDAC) and dihydrofolate reductase (DHFR), two enzymes overexpressed in metastasizing tumors. Folic Acid 36-46 dihydrofolate reductase Homo sapiens 167-190 21568878-1 2011 A set of hydroxamate derivatives of folic acid and methotrexate (MTX) was synthesized and evaluated for the inhibitory activity against histone deacetylase (HDAC) and dihydrofolate reductase (DHFR), two enzymes overexpressed in metastasizing tumors. Folic Acid 36-46 dihydrofolate reductase Homo sapiens 192-196 21179031-1 2011 BACKGROUND: Pralatrexate is a dihydrofolate reductase (DHFR) inhibitor with high affinity for reduced folate carrier 1 (RFC-1) and folylpolyglutamate synthetase (FPGS), resulting in extensive internalization and accumulation in tumour cells. Folic Acid 37-43 dihydrofolate reductase Homo sapiens 55-59 22023442-3 2011 Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), which reduces both folates and unconjugated pteridines. Folic Acid 21-28 dihydrofolate reductase Homo sapiens 59-63 22023442-3 2011 Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), which reduces both folates and unconjugated pteridines. Folic Acid 21-28 dihydrofolate reductase Homo sapiens 65-88 22023442-3 2011 Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), which reduces both folates and unconjugated pteridines. Folic Acid 180-187 dihydrofolate reductase Homo sapiens 65-88 19839929-3 2010 Polyglutamate derivatives mainly inhibit three key enzymes of intracellular folate metabolism, i.e. thymidylates synthase (TYMS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), with TYMS being the most relevant target. Folic Acid 76-82 dihydrofolate reductase Homo sapiens 130-153 21629435-4 2010 Due to the pivotal role that DHFR plays in folate metabolism and cancer treatment, changes in the level of DHFR expression can affect susceptibility to a variety of diseases dependent on folate status such as spina bifida and cancer. Folic Acid 43-49 dihydrofolate reductase Homo sapiens 29-33 21629435-4 2010 Due to the pivotal role that DHFR plays in folate metabolism and cancer treatment, changes in the level of DHFR expression can affect susceptibility to a variety of diseases dependent on folate status such as spina bifida and cancer. Folic Acid 43-49 dihydrofolate reductase Homo sapiens 107-111 21629435-4 2010 Due to the pivotal role that DHFR plays in folate metabolism and cancer treatment, changes in the level of DHFR expression can affect susceptibility to a variety of diseases dependent on folate status such as spina bifida and cancer. Folic Acid 187-193 dihydrofolate reductase Homo sapiens 29-33 21629435-4 2010 Due to the pivotal role that DHFR plays in folate metabolism and cancer treatment, changes in the level of DHFR expression can affect susceptibility to a variety of diseases dependent on folate status such as spina bifida and cancer. Folic Acid 187-193 dihydrofolate reductase Homo sapiens 107-111 21629435-5 2010 Likewise, variability in DHFR expression can affect sensitivity to anti-cancer drugs such as the folate antagonist methotrexate. Folic Acid 97-103 dihydrofolate reductase Homo sapiens 25-29 21301589-2 2010 Antifolates are inhibitors of key enzymes in folate metabolism, namely dihydrofolate reductase, beta-glycinamide ribonucleotide transformylase, 5"-amino-4"-imidazolecarboxamide ribonucleotide transformylase, and thymidylate synthetase. Folic Acid 4-10 dihydrofolate reductase Homo sapiens 71-94 19816791-3 2010 The focus of this study was to deliver the dihydrofolate reductase (DHFR) siRNA expressing plasmid and to silence the DHFR gene in FR positive KB cells, by complexing the plasmid with a folate-polyethylene glycol-polyethylenimine (FOL-PEG-PEI) conjugate, as a gene carrier. Folic Acid 50-56 dihydrofolate reductase Homo sapiens 68-72 19816791-3 2010 The focus of this study was to deliver the dihydrofolate reductase (DHFR) siRNA expressing plasmid and to silence the DHFR gene in FR positive KB cells, by complexing the plasmid with a folate-polyethylene glycol-polyethylenimine (FOL-PEG-PEI) conjugate, as a gene carrier. Folic Acid 50-56 dihydrofolate reductase Homo sapiens 118-122 21120433-0 2010 19-base pair deletion polymorphism of the dihydrofolate reductase (DHFR) gene: maternal risk of Down syndrome and folate metabolism. Folic Acid 49-55 dihydrofolate reductase Homo sapiens 67-71 21120433-2 2010 This study evaluated the influence of a 19-base pair (bp) deletion polymorphism in intron-1 of the dihydrofolate reductase (DHFR) gene on the maternal risk of DS, and investigated the association between this polymorphism and variations in the concentrations of serum folate and plasma homocysteine (Hcy) and plasma methylmalonic acid (MMA). Folic Acid 106-112 dihydrofolate reductase Homo sapiens 124-128 20424322-4 2010 The activity of folate was dependent on its activation by the enzyme dihydrofolate reductase (Dhfr) and a functional methylation cycle. Folic Acid 16-22 dihydrofolate reductase Homo sapiens 69-92 20424322-4 2010 The activity of folate was dependent on its activation by the enzyme dihydrofolate reductase (Dhfr) and a functional methylation cycle. Folic Acid 16-22 dihydrofolate reductase Homo sapiens 94-98 19839929-3 2010 Polyglutamate derivatives mainly inhibit three key enzymes of intracellular folate metabolism, i.e. thymidylates synthase (TYMS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), with TYMS being the most relevant target. Folic Acid 76-82 dihydrofolate reductase Homo sapiens 155-159 19706381-0 2009 The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Folic Acid 113-123 dihydrofolate reductase Homo sapiens 44-67 19706381-3 2009 Folic acid is a synthetic oxidized form not significantly found in fresh natural foods; to be used it must be converted to tetrahydrofolate by dihydrofolate reductase (DHFR). Folic Acid 0-10 dihydrofolate reductase Homo sapiens 143-166 19706381-3 2009 Folic acid is a synthetic oxidized form not significantly found in fresh natural foods; to be used it must be converted to tetrahydrofolate by dihydrofolate reductase (DHFR). Folic Acid 0-10 dihydrofolate reductase Homo sapiens 168-172 19706381-5 2009 Here we show, using a sensitive assay we developed, that the reduction of folic acid by DHFR per gram of human liver (n = 6) obtained from organ donors or directly from surgery is, on average, less than 2% of that in rat liver at physiological pH. Folic Acid 74-84 dihydrofolate reductase Homo sapiens 88-92 19719239-4 2009 X-ray crystal structures of 2 and 1 (the 6-methyl analogue of 2), DHFR, and NADPH showed for the first time that the thieno[2,3-d]pyrimidine ring binds in a "folate" mode. Folic Acid 158-164 dihydrofolate reductase Homo sapiens 66-70 20049736-8 2009 This suggested that the ability of methotrexate to modulate folate synthesis via inhibition of DHFR, may explain MSH2 selectivity. Folic Acid 60-66 dihydrofolate reductase Homo sapiens 95-99 19536847-0 2009 DHFR 19-bp insertion/deletion polymorphism and MTHFR C677T in adult acute lymphoblastic leukaemia: is the risk reduction due to intracellular folate unbalancing? Folic Acid 142-148 dihydrofolate reductase Homo sapiens 0-4 18247058-0 2008 An insertion/deletion polymorphism of the dihydrofolate reductase (DHFR) gene is associated with serum and red blood cell folate concentrations in women. Folic Acid 49-55 dihydrofolate reductase Homo sapiens 67-71 19174154-2 2009 This class is characterized by retention of dihydrofolate reductase (DHFR; EC 1.5.1.3) as their locus of action and transport by the reduced folate carrier (RFC; SLC19A1), but their lack of metabolism by known pathways of antifolate (e.g., methotrexate (MTX)) metabolism. Folic Acid 51-57 dihydrofolate reductase Homo sapiens 69-73 18851711-1 2009 In contrast with most species, including humans, which have monofunctional forms of the folate biosynthetic enzymes TS (thymidylate synthase) and DHFR (dihydrofolate reductase), several pathogenic protozoal parasites, including Cryptosporidium hominis, contain a bifunctional form of the enzymes on a single polypeptide chain having both catalytic activities. Folic Acid 88-94 dihydrofolate reductase Homo sapiens 146-150 18851711-1 2009 In contrast with most species, including humans, which have monofunctional forms of the folate biosynthetic enzymes TS (thymidylate synthase) and DHFR (dihydrofolate reductase), several pathogenic protozoal parasites, including Cryptosporidium hominis, contain a bifunctional form of the enzymes on a single polypeptide chain having both catalytic activities. Folic Acid 88-94 dihydrofolate reductase Homo sapiens 152-175 18247058-4 2008 The impact of the dihydrofolate reductase (DHFR) c.86 + 60_78 insertion/deletion (ins/del) polymorphism on folate and homocysteine concentrations was analyzed using data from healthy young adults from Northern Ireland, collected as part of visit three of the Young Hearts Project. Folic Acid 25-31 dihydrofolate reductase Homo sapiens 43-47 18247058-6 2008 Among women the DHFR c.86 + 60_78 polymorphism explained 2% of the variation in RBC folate levels and 5% of the variation in serum folate levels, but did not appear to have an independent effect on homocysteine. Folic Acid 84-90 dihydrofolate reductase Homo sapiens 16-20 18247058-6 2008 Among women the DHFR c.86 + 60_78 polymorphism explained 2% of the variation in RBC folate levels and 5% of the variation in serum folate levels, but did not appear to have an independent effect on homocysteine. Folic Acid 131-137 dihydrofolate reductase Homo sapiens 16-20 18247058-7 2008 Relative to women with the DHFR c.86 + 60_78 ins/ins and ins/del genotypes, del/del homozygotes had increased serum and red blood cell folate concentrations and may therefore be at decreased risk of having offspring affected by NTDs and of other adverse reproductive and health outcomes attributable to low folate. Folic Acid 135-141 dihydrofolate reductase Homo sapiens 27-31 19146480-1 2009 Plasmodium falciparum thymidylate synthase-dihydrofolate reductase (TS-DHFR) is an essential enzyme in folate biosynthesis and a major malarial drug target. Folic Acid 50-56 dihydrofolate reductase Homo sapiens 71-75 19010378-7 2009 Further work in this direction suggested that cytotoxic interaction between folate deficiency and gamma radiation might induce utilization of choline and choline containing moieties by modifying levels of key regulatory enzymes dihydrofolate reductase (DHFR) and choline oxidase (ChoOx). Folic Acid 76-82 dihydrofolate reductase Homo sapiens 228-251 19010378-7 2009 Further work in this direction suggested that cytotoxic interaction between folate deficiency and gamma radiation might induce utilization of choline and choline containing moieties by modifying levels of key regulatory enzymes dihydrofolate reductase (DHFR) and choline oxidase (ChoOx). Folic Acid 76-82 dihydrofolate reductase Homo sapiens 253-257 19022952-0 2008 A 19-base pair deletion polymorphism in dihydrofolate reductase is associated with increased unmetabolized folic acid in plasma and decreased red blood cell folate. Folic Acid 107-117 dihydrofolate reductase Homo sapiens 40-63 19022952-1 2008 Dihydrofolate reductase (DHFR) catalyzes the reduction of folic acid to tetrahydrofolate (THF). Folic Acid 58-68 dihydrofolate reductase Homo sapiens 0-23 19022952-1 2008 Dihydrofolate reductase (DHFR) catalyzes the reduction of folic acid to tetrahydrofolate (THF). Folic Acid 58-68 dihydrofolate reductase Homo sapiens 25-29 19022952-4 2008 The objective of this research was to determine the effects of the DHFR mutation with respect to folate status and assess influence of folic acid intake on these relations. Folic Acid 97-103 dihydrofolate reductase Homo sapiens 67-71 19022952-6 2008 There was a significant interaction between DHFR genotype and folic acid intake with respect to the prevalence of high circulating unmetabolized folic acid (defined as >85th percentile). Folic Acid 145-155 dihydrofolate reductase Homo sapiens 44-48 19022952-8 2008 Interaction between the DHFR polymorphism and folic acid intake was also seen with respect to RBC folate (P for interaction = 0.01). Folic Acid 46-56 dihydrofolate reductase Homo sapiens 24-28 19022952-8 2008 Interaction between the DHFR polymorphism and folic acid intake was also seen with respect to RBC folate (P for interaction = 0.01). Folic Acid 98-104 dihydrofolate reductase Homo sapiens 24-28 19022952-10 2008 Our results suggest the del/del polymorphism in DHFR is a functional polymorphism, because it limits assimilation of folic acid into cellular folate stores at high and low folic acid intakes. Folic Acid 117-127 dihydrofolate reductase Homo sapiens 48-52 19022952-10 2008 Our results suggest the del/del polymorphism in DHFR is a functional polymorphism, because it limits assimilation of folic acid into cellular folate stores at high and low folic acid intakes. Folic Acid 142-148 dihydrofolate reductase Homo sapiens 48-52 19022952-10 2008 Our results suggest the del/del polymorphism in DHFR is a functional polymorphism, because it limits assimilation of folic acid into cellular folate stores at high and low folic acid intakes. Folic Acid 172-182 dihydrofolate reductase Homo sapiens 48-52 18247058-3 2008 Dihydrofolate reductase catalyzes the reduction of folic acid to dihydrofolate and thereafter to tetrahydrofolate. Folic Acid 51-61 dihydrofolate reductase Homo sapiens 0-23 19850982-3 2008 To counteract these damage, a variety of DNA repair pathways have evolved that require regular supply of DNA bases whose biosynthesis in turn depends on sufficient pools of folate dependent enzymes like dihydrofolate reductase (DHFR). Folic Acid 173-179 dihydrofolate reductase Homo sapiens 203-226 19850982-3 2008 To counteract these damage, a variety of DNA repair pathways have evolved that require regular supply of DNA bases whose biosynthesis in turn depends on sufficient pools of folate dependent enzymes like dihydrofolate reductase (DHFR). Folic Acid 173-179 dihydrofolate reductase Homo sapiens 228-232 19850982-4 2008 In the present study, we examined the ionizing radiation mediated perturbation of DHFR activity in folate deficient and folate sufficient conditions. Folic Acid 99-105 dihydrofolate reductase Homo sapiens 82-86 19850982-4 2008 In the present study, we examined the ionizing radiation mediated perturbation of DHFR activity in folate deficient and folate sufficient conditions. Folic Acid 120-126 dihydrofolate reductase Homo sapiens 82-86 19850982-5 2008 In folate deficient animals a potent inhibition of liver DHFR activity was observed. Folic Acid 3-9 dihydrofolate reductase Homo sapiens 57-61 19850982-6 2008 Our results showed that combination of folate starvation and ionizing radiation might adversely affect the DHFR activity, compared to their individual treatments. Folic Acid 39-45 dihydrofolate reductase Homo sapiens 107-111 19850982-8 2008 In conclusion our data suggest an interactive role of folate deficiency and radiation injury in inhibiting DHFR activity. Folic Acid 54-60 dihydrofolate reductase Homo sapiens 107-111 17446168-7 2007 The three folate-dependent enzymes that constitute the de novo thymidylate biosynthesis pathway, cSHMT, thymidylate synthase, and dihydrofolate reductase, all contain SUMO modification consensus sequences. Folic Acid 10-16 dihydrofolate reductase Homo sapiens 130-153 17597297-0 2007 Preliminary evidence for involvement of the folate gene polymorphism 19bp deletion-DHFR in occurrence of autism. Folic Acid 44-50 dihydrofolate reductase Homo sapiens 83-87 17597297-5 2007 Here, we report that the 19bp-deletion polymorphism of DHFR acts independently (OR 2.69, 95% CI; 1.00-7.28, p<0.05) and in concert with related folate polymorphisms as a significant risk factor for autism. Folic Acid 144-150 dihydrofolate reductase Homo sapiens 55-59 16969375-2 2007 The gene dihydrofolate reductase (DHFR) is primarily involved in the reduction of dihydrofolate, generated during thymidylate synthesis, to tetrahydrofolate in order to maintain adequate amounts of folate for DNA synthesis and homocysteine remethylation. Folic Acid 16-22 dihydrofolate reductase Homo sapiens 34-38 17336564-1 2007 The dihydrofolate reductase (DHFR) enzyme is important for folate availability, folate turnover and DNA synthesis. Folic Acid 11-17 dihydrofolate reductase Homo sapiens 29-33 17336564-1 2007 The dihydrofolate reductase (DHFR) enzyme is important for folate availability, folate turnover and DNA synthesis. Folic Acid 59-65 dihydrofolate reductase Homo sapiens 4-27 17336564-1 2007 The dihydrofolate reductase (DHFR) enzyme is important for folate availability, folate turnover and DNA synthesis. Folic Acid 59-65 dihydrofolate reductase Homo sapiens 29-33 17413111-2 2007 Folic acid from multivitamins needs to be reduced by DHFR before it participates in cellular reactions. Folic Acid 0-10 dihydrofolate reductase Homo sapiens 53-57 17486595-2 2007 This has focused attention on folate-related genes such as dihydrofolate reductase (DHFR) in a bid to identify the genetic factors that influence NTD risk through either the fetal or maternal genotype. Folic Acid 30-36 dihydrofolate reductase Homo sapiens 59-82 17486595-2 2007 This has focused attention on folate-related genes such as dihydrofolate reductase (DHFR) in a bid to identify the genetic factors that influence NTD risk through either the fetal or maternal genotype. Folic Acid 30-36 dihydrofolate reductase Homo sapiens 84-88 17661690-1 2006 Folate metabolism of the malaria parasites provides two targets for current antimalarials: dihydrofolate reductase and dihydropteroate synthase. Folic Acid 0-6 dihydrofolate reductase Homo sapiens 91-114 16712799-10 2006 FDH-resistant cells have strongly up-regulated dihydrofolate reductase (DHFR) that is proposed to be a mechanism for the alteration of folate pools and a key component of the acquired resistance. Folic Acid 54-60 dihydrofolate reductase Homo sapiens 72-76 16790925-2 2006 The amino-acid sequence and molecular architecture of R67 DHFR and its inhibitory properties toward folate analogues are different from those of chromosomal DHFR. Folic Acid 100-106 dihydrofolate reductase Homo sapiens 58-62 14690438-10 2003 Binding of the folate analogue methotrexate favors a stable three-dimensional structure of the dihydrofolate reductase domain. Folic Acid 15-21 dihydrofolate reductase Homo sapiens 95-118 15755837-2 2005 Dihydrofolate reductase (DHFR) is required to convert the folic acid used in supplements and for food fortification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced folate forms used by the cell. Folic Acid 58-68 dihydrofolate reductase Homo sapiens 0-23 15755837-2 2005 Dihydrofolate reductase (DHFR) is required to convert the folic acid used in supplements and for food fortification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced folate forms used by the cell. Folic Acid 58-68 dihydrofolate reductase Homo sapiens 25-29 15755837-2 2005 Dihydrofolate reductase (DHFR) is required to convert the folic acid used in supplements and for food fortification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced folate forms used by the cell. Folic Acid 7-13 dihydrofolate reductase Homo sapiens 25-29 15504856-1 2004 Most drugs used for prevention and treatment of Pneumocystis jirovecii pneumonia target enzymes involved in the biosynthesis of folic acid, i.e., dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). Folic Acid 128-138 dihydrofolate reductase Homo sapiens 207-211 15182183-17 2004 Isothermal titration calorimetry studies were also conducted on many of the mutants described above to determine the enthalpy of folate binding to the R67 DHFR.NADPH complex. Folic Acid 129-135 dihydrofolate reductase Homo sapiens 155-159 14735580-10 2004 About half of dietary folates and all of folic acid supplements must be reduced by DHFR to be available for mother and fetus. Folic Acid 22-29 dihydrofolate reductase Homo sapiens 83-87 14735580-10 2004 About half of dietary folates and all of folic acid supplements must be reduced by DHFR to be available for mother and fetus. Folic Acid 41-51 dihydrofolate reductase Homo sapiens 83-87 14705776-11 2003 This analysis affords a new analytical assay for the dihydrofolate reductase-catalyzed reaction and several dehydrogenases involved in folic acid metabolism. Folic Acid 135-145 dihydrofolate reductase Homo sapiens 53-76 12851689-8 2003 In HCT-8 and DW2 cells at 2.3 and 40 micro M PteGlu, inhibition of DHFR by TMQ induced antithymidylate and antipurine effects; AG2034 and RTX selectively inhibited de novo purine or thymidine synthesis, respectively. Folic Acid 45-51 dihydrofolate reductase Homo sapiens 67-71 14502550-1 2003 Pyrimethamine, an antimalarial drug, was found to be able to inhibit both enzymes (DHFR-TS and PTR1) of the leishmanial folate pathway, although this effect in vivo appears only in relatively high concentrations. Folic Acid 120-126 dihydrofolate reductase Homo sapiens 83-87 12851689-11 2003 These results further substantiate the hypothesis that the nonpolyglutamylatable DHFR inhibitor, TMQ, acts as a modulator by decreasing the protection by PteGlu of cells against the polyglutamylatable AG2034 and RTX. Folic Acid 154-160 dihydrofolate reductase Homo sapiens 81-85 12583828-4 2003 Methotrexate inhibits dihydrofolate reductase, which leads to accumulation of polyglutamated folates, causing further inhibition of thymidylate synthase and glycinamide ribonucleotide formyltransferase. Folic Acid 93-100 dihydrofolate reductase Homo sapiens 22-45 12482753-2 2003 DHFR retains the capacity to bind folate analogues in the lumen of microsomes and in the ER of intact cells, upon which it acquires a conformation resistant to proteinase K digestion. Folic Acid 34-40 dihydrofolate reductase Homo sapiens 0-4 12482753-5 2003 In fact, a slight acceleration of the dislocation of DHFR heavy chain fusion was observed in vitro in the presence of a folate analogue. Folic Acid 120-126 dihydrofolate reductase Homo sapiens 53-57 11774738-2 2001 The cells acquired resistance to antifolate drug(s) through: (1) impaired drug uptake via the reduced folate carrier, (2) increased activity of the target enzymes[dihydrofolate reductase(DHFR) or thymidylate synthase(TS)] resulted from a concomitant amplification and overexpression of their gene, (3) induction of a variant DHFR with a low affinity for antifolate drug(s) used for the selection of resistance, and (4) defective polyglutamation. Folic Acid 37-43 dihydrofolate reductase Homo sapiens 325-329 11989624-6 2001 The bound pteridine ring of folate (Fol I) from the crystal structure of R67 DHFR was used as the basis for docking the nicotinamide-ribose-Pi (NMN) moiety of NADPH. Folic Acid 28-34 dihydrofolate reductase Homo sapiens 77-81 11774738-2 2001 The cells acquired resistance to antifolate drug(s) through: (1) impaired drug uptake via the reduced folate carrier, (2) increased activity of the target enzymes[dihydrofolate reductase(DHFR) or thymidylate synthase(TS)] resulted from a concomitant amplification and overexpression of their gene, (3) induction of a variant DHFR with a low affinity for antifolate drug(s) used for the selection of resistance, and (4) defective polyglutamation. Folic Acid 37-43 dihydrofolate reductase Homo sapiens 187-191 11962509-0 2001 Investigations on the biological properties of the lipophilic DHFR-inhibitory benzoprims reveal non-folate modes of action and opportunities for anti-cancer drug design. Folic Acid 100-106 dihydrofolate reductase Homo sapiens 62-66 11284680-19 2001 Analogous NMR studies performed on folate, DMDDF, and R67 DHFR indicate formation of a ternary complex in which two symmetry-related binding sites are occupied by folate and DMDDF. Folic Acid 163-169 dihydrofolate reductase Homo sapiens 58-62 11284680-4 2001 Although the crystal structure of the complex of R67 DHFR with folate has been reported [Narayana et al. Folic Acid 63-69 dihydrofolate reductase Homo sapiens 53-57 11509884-2 2001 Among them, dihydrofolate reductase (DHFR) and thymidylate synthase (TS) require folate as coenzymes. Folic Acid 19-25 dihydrofolate reductase Homo sapiens 37-41 11996001-1 2001 Dihydrofolate reductase (DHFR, EC 1.5.1.3) is one of the enzymes active in the folate cycle which plays an important role in DNA synthesis. Folic Acid 7-13 dihydrofolate reductase Homo sapiens 25-29 11509884-4 2001 Polyglutamated folates are selectively retained within the cell and have an increased affinity for DHFR and TS. Folic Acid 15-22 dihydrofolate reductase Homo sapiens 99-103 10739874-1 2000 N(alpha)-(4-Amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-o rnithine (PT523) is an unusually tight-binding dihydrofolate reductase (DHFR) inhibitor and is efficiently taken up into cells via the reduced folate carrier (RFC). Folic Acid 115-121 dihydrofolate reductase Homo sapiens 133-137 10993224-8 2000 These results demonstrate that the potent inhibitory activities of N(omega)-masked ornithine analogs against the growth of Meth A cells and methotrexate-resistant CCRF-CEM cells, results from effective uptake via reduced folate carrier and their potent DHFR inhibition. Folic Acid 221-227 dihydrofolate reductase Homo sapiens 253-257 10683342-7 2000 KSHV-DHFR was inhibited by folate antagonists such as methotrexate (K(i): 200 pM), aminopterin (K(i): 610 pM), pyrimethamine (K(i): 29 nM), trimethoprim (K(i): 2.3 microM), and piritrexim (K(i): 3.9 nM). Folic Acid 27-33 dihydrofolate reductase Homo sapiens 5-9 10683342-8 2000 In all cases, K(i) values for these folate antagonists were higher for KSHV-DHFR than for rhDHFR. Folic Acid 36-42 dihydrofolate reductase Homo sapiens 76-80 10584062-1 1999 We have investigated the importance of polarization by the enzyme dihydrofolate reductase (DHFR) on its substrates, folate and dihydrofolate, using a series of quantum mechanical (QM) techniques (Hartree-Fock (HF), Moller-Plesset second-order perturbation theory (MP2), local density approximation (LDA) and generalized gradient approximation (GGA) density functional theory (DFT) calculations) in which the bulk enzyme is included in the calculations as point charges. Folic Acid 73-79 dihydrofolate reductase Homo sapiens 91-95 10499129-2 1998 In this application, pulsed ultrafiltration conditions were optimized for the isolation and identification of inhibitors of dihydrofolate reductase from a 22 compound library containing six known inhibitors of the enzyme including trimethoprim, aminopterin, methotrexate, pyrimethamine, folic acid, and folinic acid, and 16 compounds without known affinity. Folic Acid 287-297 dihydrofolate reductase Homo sapiens 124-147 9723869-1 1998 When maintained under continuous selection with the folate inhibitor, methotrexate, cultured Aedes albopicfus mosquito cells amplify an 200 kb region of DNA containing the dihydrofolate reductase gene. Folic Acid 52-58 dihydrofolate reductase Homo sapiens 172-195 9952321-1 1999 Folic acid (PteGlu)-enhanced intense synergy has been observed between nonpolyglutamylatable dihydrofolate reductase (DHFR) inhibitors and polyglutamylatable inhibitors of other folate-requiring enzymes, such as glycinamide ribonucleotide formyltransferase (GARFT) and thymidylate synthase. Folic Acid 0-10 dihydrofolate reductase Homo sapiens 93-116 9952321-1 1999 Folic acid (PteGlu)-enhanced intense synergy has been observed between nonpolyglutamylatable dihydrofolate reductase (DHFR) inhibitors and polyglutamylatable inhibitors of other folate-requiring enzymes, such as glycinamide ribonucleotide formyltransferase (GARFT) and thymidylate synthase. Folic Acid 0-10 dihydrofolate reductase Homo sapiens 118-122 9952321-1 1999 Folic acid (PteGlu)-enhanced intense synergy has been observed between nonpolyglutamylatable dihydrofolate reductase (DHFR) inhibitors and polyglutamylatable inhibitors of other folate-requiring enzymes, such as glycinamide ribonucleotide formyltransferase (GARFT) and thymidylate synthase. Folic Acid 12-18 dihydrofolate reductase Homo sapiens 93-116 9952321-1 1999 Folic acid (PteGlu)-enhanced intense synergy has been observed between nonpolyglutamylatable dihydrofolate reductase (DHFR) inhibitors and polyglutamylatable inhibitors of other folate-requiring enzymes, such as glycinamide ribonucleotide formyltransferase (GARFT) and thymidylate synthase. Folic Acid 12-18 dihydrofolate reductase Homo sapiens 118-122 9857014-4 1998 The thylakoidal system is able to transport dihydrofolate reductase (DHFR) when an appropriate signal is attached, and the transport efficiency is almost undiminished by the binding of folate analogs such as methotrexate that cause the protein to fold very tightly. Folic Acid 51-57 dihydrofolate reductase Homo sapiens 69-73 9679969-8 1998 Thus, the ideal requirement for the folic acid-enhanced synergy is that a nonpolyglutamylatable DHFR inhibitor be combined with a polyglutamylatable inhibitor of another folate-requiring enzyme. Folic Acid 36-46 dihydrofolate reductase Homo sapiens 96-100 9679969-9 1998 A hypothesis to explain this general phenomenon involves the critical role of folylpoly-gamma-glutamate synthetase and the effect of the DHFR inhibitor in decreasing the protection by folic acid of cells to the other antifolates. Folic Acid 184-194 dihydrofolate reductase Homo sapiens 137-141 9762364-1 1998 Chemotherapeutic drugs targeted at folate-dependent reactions have typically been directed at a limited number of target enzymes: dihydrofolate reductase, thymidylate synthase, and GAR and AICAR transformylase. Folic Acid 35-41 dihydrofolate reductase Homo sapiens 130-153 8164259-11 1994 Further evaluation of the cytotoxicity of 1 and 2 in CCRF-CEM cells and its sublines, having defined mechanisms of methotrexate (MTX) resistance, demonstrated that the analogues utilize the reduced folate/MTX-transport system and primarily inhibit DHFR and that poly-gamma-glutamylation was crucial to their mechanism of action. Folic Acid 198-204 dihydrofolate reductase Homo sapiens 248-252 9479873-8 1997 Selective inhibitors of TS with a folate structure such as raltitrexed could circumvent the resistance by virtue of DHFR overproduction, and this class of compounds which have higher substrate activities for FPGS than MTX may be of value for the treatment of myeloid leukemias in addition to lymphocytic malignancies resistant to conventional chemotherapy. Folic Acid 34-40 dihydrofolate reductase Homo sapiens 116-120 9012448-1 1997 Mutations in the enzyme dihydrofolate reductase (DHFR) can confer resistance to the inhibitory effects of folate analogs such as methotrexate (Mtx) and trimetrexate (Ttx). Folic Acid 31-37 dihydrofolate reductase Homo sapiens 49-53 8978793-2 1996 Methotrexate tightly binds to dihydrofolate reductase (DHFR), blocking the reduction of dihydrofolate to tetrahydrofolic acid, the active form of folic acid. Folic Acid 115-125 dihydrofolate reductase Homo sapiens 30-53 8978793-2 1996 Methotrexate tightly binds to dihydrofolate reductase (DHFR), blocking the reduction of dihydrofolate to tetrahydrofolic acid, the active form of folic acid. Folic Acid 115-125 dihydrofolate reductase Homo sapiens 55-59 8527095-3 1995 DESIGN AND METHODS: We constructed a chimeric protein between Tat and dihydrofolate reductase (DHFR), a cytosolic enzyme that binds tightly to the folate analogue methotrexate (MTX). Folic Acid 77-83 dihydrofolate reductase Homo sapiens 95-99 8913793-1 1996 MX-68 is a newly synthesized anti-folate, chemically designed not to undergo intracellular polyglutamation and to have increased affinity to dihydrofolate reductase (DHFR). Folic Acid 34-40 dihydrofolate reductase Homo sapiens 166-170 7783147-8 1995 Further evaluation of 9 against CCRF-CEM and its sublines having defined mechanisms of MTX resistance demonstrated that the analogue utilizes the reduced folate/MTX-transport system and primarily inhibits DHFR and poly-gamma-glutamylation plays a role in its mechanism of action. Folic Acid 154-160 dihydrofolate reductase Homo sapiens 205-209 8852336-2 1995 The primary target of MTX is the enzyme dihydrofolate reductase (DHFR) which catalyzes the reduction of folate and 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate. Folic Acid 47-53 dihydrofolate reductase Homo sapiens 65-69 1904273-1 1991 A fluorescein derivative of the lysine analogue of folic acid, N alpha-pteroyl-N epilson-(4"-fluoresceinthiocarbamoyl)-L-lysine (PLF), was synthesized as a probe for dihydrofolate reductase (DHFR) and a membrane folate binding protein (m-FBP). Folic Acid 51-61 dihydrofolate reductase Homo sapiens 166-189 8361048-1 1993 Three methods for analyzing the products of polymerase chain reaction were applied to detect complex alterations of dihydrofolate reductase (DHFR) gene, in order to assess their value in detection of folate-resistance in leukemia cells. Folic Acid 123-129 dihydrofolate reductase Homo sapiens 141-145 8449831-1 1993 In order to clarify a molecular mechanism of folate resistance in leukemia cells, we studied alterations of the dihydrofolate reductase (DHFR) gene in a human leukemia cell line, MOLT-3, and its sublines made resistant to methotrexate (MTX), trimetrexate (TMQ) and N10-propargyl-5,8-dideazafolic acid (CB3717), alone or in combination. Folic Acid 45-51 dihydrofolate reductase Homo sapiens 137-141 1529671-1 1992 Dihydrofolate reductase (DHFR, EC 1.5.1.3) is an enzyme involved in the metabolism of nucleic acids; it is also an important target for folate antagonists such as methotrexate (MTX). Folic Acid 7-13 dihydrofolate reductase Homo sapiens 25-29 7942284-7 1994 Although DHFR is an extremely well-studied enzyme, there is still some uncertainty about its kinetics, mechanism for reduction of folate, multiple forms, and activation by a diverse group of agents. Folic Acid 130-136 dihydrofolate reductase Homo sapiens 9-13 8195828-4 1993 Many folate analogues are competitive inhibitors of DHFR, and while some classes show no selectivity, suitably substituted diaminopyrimidines are several thousands times more active against bacterial than mammalian DHFR and are thus effective and safe antibiotics. Folic Acid 5-11 dihydrofolate reductase Homo sapiens 52-56 8195828-4 1993 Many folate analogues are competitive inhibitors of DHFR, and while some classes show no selectivity, suitably substituted diaminopyrimidines are several thousands times more active against bacterial than mammalian DHFR and are thus effective and safe antibiotics. Folic Acid 5-11 dihydrofolate reductase Homo sapiens 215-219 8449831-8 1993 These data suggest that complex alterations of the DHFR gene are involved in the molecular mechanisms of folate resistance that can be differentially introduced into leukemia cells by exposure to various folate analogues, alone or in combination. Folic Acid 105-111 dihydrofolate reductase Homo sapiens 51-55 8449831-8 1993 These data suggest that complex alterations of the DHFR gene are involved in the molecular mechanisms of folate resistance that can be differentially introduced into leukemia cells by exposure to various folate analogues, alone or in combination. Folic Acid 204-210 dihydrofolate reductase Homo sapiens 51-55 1637816-1 1992 The kinetics of the NADPH-dependent reduction of 7,8-dihydrofolate, folate, and 7,8-dihydrobiopterin by human dihydrofolate reductase have been examined over the pH range from 4.0 to 9.5. Folic Acid 60-66 dihydrofolate reductase Homo sapiens 110-133 1314649-0 1992 Effect of enzyme and ligand protonation on the binding of folates to recombinant human dihydrofolate reductase: implications for the evolution of eukaryotic enzyme efficiency. Folic Acid 58-65 dihydrofolate reductase Homo sapiens 87-110 1314649-4 1992 koff for dissociation of folate, dihydrofolate (H2folate), and H4folate from their binary complexes with hDHFR is similarly pH dependent. Folic Acid 25-31 dihydrofolate reductase Homo sapiens 105-110 1768284-3 1991 The significantly lower activity of both compounds under folate-independent conditions indicated DHFR as the primary target. Folic Acid 57-63 dihydrofolate reductase Homo sapiens 97-101 1907850-1 1991 Arginine-70 of human dihydrofolate reductase (hDHFR) is a highly conserved residue which X-ray crystallographic data have shown to interact with the alpha-carboxylate of the terminal L-glutamate moiety of either folic acid or methotrexate (MTX). Folic Acid 212-222 dihydrofolate reductase Homo sapiens 21-44 1907850-1 1991 Arginine-70 of human dihydrofolate reductase (hDHFR) is a highly conserved residue which X-ray crystallographic data have shown to interact with the alpha-carboxylate of the terminal L-glutamate moiety of either folic acid or methotrexate (MTX). Folic Acid 212-222 dihydrofolate reductase Homo sapiens 46-51 1904273-1 1991 A fluorescein derivative of the lysine analogue of folic acid, N alpha-pteroyl-N epilson-(4"-fluoresceinthiocarbamoyl)-L-lysine (PLF), was synthesized as a probe for dihydrofolate reductase (DHFR) and a membrane folate binding protein (m-FBP). Folic Acid 51-61 dihydrofolate reductase Homo sapiens 191-195 1904273-6 1991 The dissociation constant for the fluorescein derivative with respect to human DHFR is 115 nM as compared to 111 nM for folic acid. Folic Acid 120-130 dihydrofolate reductase Homo sapiens 79-83 1904273-7 1991 The Ki value for the competitive inhibition of human DHFR by the fluorescent analogue of folic acid is 2.0 microM compared to 0.48 microM for folic acid. Folic Acid 89-99 dihydrofolate reductase Homo sapiens 53-57 1904273-7 1991 The Ki value for the competitive inhibition of human DHFR by the fluorescent analogue of folic acid is 2.0 microM compared to 0.48 microM for folic acid. Folic Acid 142-152 dihydrofolate reductase Homo sapiens 53-57 2180768-10 1990 Interestingly, pyrimethamine-resistant strains of P. falciparum all have a common point mutation in the DHFR coding sequence (Thr/Ser 108 to Asn), which causes decreased binding of the folate analog. Folic Acid 185-191 dihydrofolate reductase Homo sapiens 104-108 2248959-1 1990 The 2.3-A crystal structure of recombinant human dihydrofolate reductase (EC 1.5.1.3, DHFR) has been solved as a binary complex with folate (a poor substrate at neutral pH) and also as a binary complex with an inhibitor, 5-deazafolate. Folic Acid 56-62 dihydrofolate reductase Homo sapiens 86-90 2178951-7 1990 Anti-folates commonly used to treat microbial infections are poor inhibitors of L. major DHFR. Folic Acid 5-12 dihydrofolate reductase Homo sapiens 89-93 2006139-1 1991 The migration of electron density of a substrate (folate) on binding to an enzyme (dihydrofolate reductase) is studied by a quantum-mechanical method originally developed in solid state physics. Folic Acid 50-56 dihydrofolate reductase Homo sapiens 83-106 2260989-9 1990 With exposure to concentrations of leucovorin capable of rescue, the individual folate pool levels were up to twelve times greater than those found in untreated cells, consistent with competition for catalytic activity at folate-dependent enzymes in addition to dihydrofolate reductase. Folic Acid 80-86 dihydrofolate reductase Homo sapiens 262-285 2178951-10 1990 Interestingly, pyrimethamine-resistant strains of P. falciparum have a common point mutation in the DHFR coding sequence which causes decreased binding of the folate analog. Folic Acid 159-165 dihydrofolate reductase Homo sapiens 100-104 2180768-7 1990 Anti-folates commonly used to treat microbial infections are poor inhibitors of L. major DHFR. Folic Acid 5-12 dihydrofolate reductase Homo sapiens 89-93 34825630-1 2021 Resistance to folate antagonists is caused by mutations in the dihydrofolate reductase (DHFR) genes. Folic Acid 14-20 dihydrofolate reductase Homo sapiens 63-86 34953855-8 2022 We identified human dihydrofolate reductase (DHFR) as a target of pyrimethamine and demonstrated that the STAT3-inhibitory effects of pyrimethamine are the result of a deficiency in reduced folate downstream of DHFR inhibition, implicating folate metabolism in the regulation of STAT3 transcriptional activity. Folic Acid 190-196 dihydrofolate reductase Homo sapiens 20-43 34953855-8 2022 We identified human dihydrofolate reductase (DHFR) as a target of pyrimethamine and demonstrated that the STAT3-inhibitory effects of pyrimethamine are the result of a deficiency in reduced folate downstream of DHFR inhibition, implicating folate metabolism in the regulation of STAT3 transcriptional activity. Folic Acid 190-196 dihydrofolate reductase Homo sapiens 45-49 34953855-8 2022 We identified human dihydrofolate reductase (DHFR) as a target of pyrimethamine and demonstrated that the STAT3-inhibitory effects of pyrimethamine are the result of a deficiency in reduced folate downstream of DHFR inhibition, implicating folate metabolism in the regulation of STAT3 transcriptional activity. Folic Acid 190-196 dihydrofolate reductase Homo sapiens 211-215 34953855-8 2022 We identified human dihydrofolate reductase (DHFR) as a target of pyrimethamine and demonstrated that the STAT3-inhibitory effects of pyrimethamine are the result of a deficiency in reduced folate downstream of DHFR inhibition, implicating folate metabolism in the regulation of STAT3 transcriptional activity. Folic Acid 240-246 dihydrofolate reductase Homo sapiens 20-43 34953855-8 2022 We identified human dihydrofolate reductase (DHFR) as a target of pyrimethamine and demonstrated that the STAT3-inhibitory effects of pyrimethamine are the result of a deficiency in reduced folate downstream of DHFR inhibition, implicating folate metabolism in the regulation of STAT3 transcriptional activity. Folic Acid 240-246 dihydrofolate reductase Homo sapiens 45-49 34710812-1 2021 Human dihydrofolate reductase (DHFR) is a conserved enzyme that is central to folate metabolism and is widely targeted in pathogenic diseases as well as cancers. Folic Acid 78-84 dihydrofolate reductase Homo sapiens 6-29 34710812-1 2021 Human dihydrofolate reductase (DHFR) is a conserved enzyme that is central to folate metabolism and is widely targeted in pathogenic diseases as well as cancers. Folic Acid 78-84 dihydrofolate reductase Homo sapiens 31-35 34464807-6 2022 In addition, some heterotrophic bacteria cooperating with AnAOB (Comamonas and Simplicispira) were found more active in R1 than that of R2 due to the higher relative abundance of functional genes related to folic acid metabolic (Dihydrofolate synthase and Dihydrofolate reductase). Folic Acid 207-217 dihydrofolate reductase Homo sapiens 256-279 34825630-1 2021 Resistance to folate antagonists is caused by mutations in the dihydrofolate reductase (DHFR) genes. Folic Acid 14-20 dihydrofolate reductase Homo sapiens 88-92 6661412-3 1983 Comparison of certain folate-requiring enzymes from crude extracts of the parent and resistant cells showed a 240-fold elevation of dihydrofolate reductase activity in the resistant cells with no significant increase in the levels of the other enzymes. Folic Acid 22-28 dihydrofolate reductase Homo sapiens 132-155 34829516-4 2021 Moreover, dihydrofolate reductase (DHFR), a key enzyme in folate-mediated metabolism, exhibited impaired activity and decreased protein expression in CRIF1 knockdown endothelial cells. Folic Acid 58-64 dihydrofolate reductase Homo sapiens 10-33 34829516-4 2021 Moreover, dihydrofolate reductase (DHFR), a key enzyme in folate-mediated metabolism, exhibited impaired activity and decreased protein expression in CRIF1 knockdown endothelial cells. Folic Acid 58-64 dihydrofolate reductase Homo sapiens 35-39 34412467-1 2021 As we all know, inhibiting the activity of dihydrofolate reductase (DHFR) has always been an effective strategy for folate antimetabolites to treat tumors. Folic Acid 116-122 dihydrofolate reductase Homo sapiens 43-66 34412467-1 2021 As we all know, inhibiting the activity of dihydrofolate reductase (DHFR) has always been an effective strategy for folate antimetabolites to treat tumors. Folic Acid 116-122 dihydrofolate reductase Homo sapiens 68-72 35253073-3 2022 The enzymes Dihydrofolate reductase, thymidylate synthase, and Serine hydroxy methyltransferase play an essential role in the folate pathway. Folic Acid 126-132 dihydrofolate reductase Homo sapiens 12-35 3339615-0 1988 Inhibition of murine thymidylate synthase and human dihydrofolate reductase by 5,8-dideaza analogues of folic acid and aminopterin. Folic Acid 104-114 dihydrofolate reductase Homo sapiens 52-75 2448654-6 1987 Important elements in leucovorin rescue are reactivation of DHFR with depression of cellular dihydrofolate (FH2) and provision of folate substrate to circumvent the block in FH4 synthesis. Folic Acid 100-106 dihydrofolate reductase Homo sapiens 60-64 6193143-2 1983 Methotrexate (MTX-Glu1) exerts its antitumor effects through its potent inhibition of dihydrofolate reductase (DHFR), the enzyme responsible for maintaining the cellular pool of reduced folates. Folic Acid 186-193 dihydrofolate reductase Homo sapiens 86-109 6193143-2 1983 Methotrexate (MTX-Glu1) exerts its antitumor effects through its potent inhibition of dihydrofolate reductase (DHFR), the enzyme responsible for maintaining the cellular pool of reduced folates. Folic Acid 186-193 dihydrofolate reductase Homo sapiens 111-115 7140422-2 1982 Antifolate activity was measured by the deoxyuridine suppression assay, direct measurement of dihydrofolate reductase and morphological changes characteristic of folate deficiency. Folic Acid 4-10 dihydrofolate reductase Homo sapiens 94-117 6882460-7 1983 The observation that NADH supports the reduction of folate and dihydrofolate but not MTX binding suggests that natural resistance to MTX could exist if NADH replaces NADPH as the main cofactor for DHFR. Folic Acid 52-58 dihydrofolate reductase Homo sapiens 197-201 7140422-8 1982 Crude X-methyl folate (2X10(-1) M) is a weak folate antagonist as compared to methotrexate since it requires a 1,000-fold higher concentration to inhibit cell growth and dihydrofolate reductase activity. Folic Acid 15-21 dihydrofolate reductase Homo sapiens 170-193 7423195-5 1980 The folic acid pteridine and phenyl rings interact in a stacking manner which is suggestive of the type of associations these groups could form in a complex of folate, dihydrofolate reductase, and reduced nicotinamide adenine dinucleotide phosphate. Folic Acid 4-14 dihydrofolate reductase Homo sapiens 168-191 109617-6 1979 These results strongly suggest that 4 can substitute for folate derivatives as cofactors for serine transhydroxymethylase, thymidylate synthetase, and dihydrofolate reductase. Folic Acid 57-63 dihydrofolate reductase Homo sapiens 93-174 33904374-1 2021 Among the various known targets for the treatment of Leishmaniasis, dihydrofolate reductase (DHFR) is an essential target which plays an important role in the folate metabolic pathway. Folic Acid 75-81 dihydrofolate reductase Homo sapiens 93-97 814898-0 1976 Interaction of 13C-enriched folate with dihydrofolate reductase studies by carbon magnetic resonance spectroscopy. Folic Acid 28-34 dihydrofolate reductase Homo sapiens 40-63 31443485-11 2019 The opposite effect DHFR promoter variant has in tuning ALL onset-time depending on who is the carrier (i.e., mother or child) might suggest a parent-origin-effect of the D-allele or a two-faced epigenetic role driven by unbalanced folate isoform availability during the in-utero leukemogenesis responsible for the wide postnatal childhood ALL latency. Folic Acid 232-238 dihydrofolate reductase Homo sapiens 20-24 32319147-1 2020 OBJECTIVE: DHFR encodes dihydrofolate reductase, a major enzyme in the metabolism of folate, and is a candidate gene for ischemic stroke (IS). Folic Acid 31-37 dihydrofolate reductase Homo sapiens 11-15 32752079-2 2020 A known folate antagonist, methotrexate (MTX) inhibits human dihydrofolate reductase (hDHFR), the enzyme responsible for the catalysis of 7,8-dihydrofolate reduction to 5,6,7,8-tetrahydrofolate, in biosynthesis and cell proliferation. Folic Acid 8-14 dihydrofolate reductase Homo sapiens 61-84 32752079-2 2020 A known folate antagonist, methotrexate (MTX) inhibits human dihydrofolate reductase (hDHFR), the enzyme responsible for the catalysis of 7,8-dihydrofolate reduction to 5,6,7,8-tetrahydrofolate, in biosynthesis and cell proliferation. Folic Acid 8-14 dihydrofolate reductase Homo sapiens 86-91 31542479-4 2019 Here we found that the expression of dihydrofolate reductase (DHFR) and thymidylate synthetase (TYMS), which played an essential role in folate metabolism and several types of tumors, were up-regulated in both human glioma tissues and cell lines, and overexpression of DHFR/TYMS promoted the proliferation of glioma cells. Folic Acid 44-50 dihydrofolate reductase Homo sapiens 62-66 31542479-4 2019 Here we found that the expression of dihydrofolate reductase (DHFR) and thymidylate synthetase (TYMS), which played an essential role in folate metabolism and several types of tumors, were up-regulated in both human glioma tissues and cell lines, and overexpression of DHFR/TYMS promoted the proliferation of glioma cells. Folic Acid 44-50 dihydrofolate reductase Homo sapiens 269-273 32820034-2 2021 Mutations in several folate pathway genes, including FOLR1 (folate receptor alpha, FRalpha), DHFR (dihydrofolate reductase) and PCFT (proton coupled folate transporter) have been previously identified in patients with CFD.Methods In an effort to identify causal mutations for CFD, we performed whole exome sequencing analysis on eight CFD trios and identified eight de novo mutations in seven trios.Results Notably, we found a de novo stop gain mutation in the capicua (CIC) gene. Folic Acid 21-27 dihydrofolate reductase Homo sapiens 93-97 32820034-2 2021 Mutations in several folate pathway genes, including FOLR1 (folate receptor alpha, FRalpha), DHFR (dihydrofolate reductase) and PCFT (proton coupled folate transporter) have been previously identified in patients with CFD.Methods In an effort to identify causal mutations for CFD, we performed whole exome sequencing analysis on eight CFD trios and identified eight de novo mutations in seven trios.Results Notably, we found a de novo stop gain mutation in the capicua (CIC) gene. Folic Acid 21-27 dihydrofolate reductase Homo sapiens 99-122 32498709-2 2020 We thus wished to determine whether the inefficiency in folate metabolism caused by genetic variation in the MTHFR and DHFR genes in folate metabolism, or inadequate folate intake, is associated with obesity. Folic Acid 56-62 dihydrofolate reductase Homo sapiens 119-123 32498709-2 2020 We thus wished to determine whether the inefficiency in folate metabolism caused by genetic variation in the MTHFR and DHFR genes in folate metabolism, or inadequate folate intake, is associated with obesity. Folic Acid 133-139 dihydrofolate reductase Homo sapiens 119-123 32498709-2 2020 We thus wished to determine whether the inefficiency in folate metabolism caused by genetic variation in the MTHFR and DHFR genes in folate metabolism, or inadequate folate intake, is associated with obesity. Folic Acid 133-139 dihydrofolate reductase Homo sapiens 119-123 31920364-3 2019 The aim of the study was to investigate the effect of folate metabolizing genes (MTHFR and DHFR) polymorphisms on different parameters of complete blood count in patients who were treated with carbamazepine and valproic acid. Folic Acid 54-60 dihydrofolate reductase Homo sapiens 91-95 31401334-2 2019 Dihydrofolate reductase (DHFR), an enzyme involved in folate metabolism converts dihydrofolate into tetrahydrofolate, which is required for the de novo synthesis of purines, and certain amino acids. Folic Acid 7-13 dihydrofolate reductase Homo sapiens 25-29 31058257-3 2019 Here we show that any one of these routes can support cell growth, but the oxPPP is uniquely required to maintain a normal NADPH/NADP ratio, mammalian dihydrofolate reductase (DHFR) activity and folate metabolism. Folic Acid 158-164 dihydrofolate reductase Homo sapiens 176-180 29708443-1 2018 OBJECTIVE: Previous studies have not used family-based methods to evaluate maternal-paternal genetic effects of the folate metabolizing enzyme, dihydro folate reductase (DHFR) essential during embryogenesis. Folic Acid 116-122 dihydrofolate reductase Homo sapiens 144-168 29708443-1 2018 OBJECTIVE: Previous studies have not used family-based methods to evaluate maternal-paternal genetic effects of the folate metabolizing enzyme, dihydro folate reductase (DHFR) essential during embryogenesis. Folic Acid 116-122 dihydrofolate reductase Homo sapiens 170-174