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DHFR Gene Record

  • Summary
  • Interactions
  • Claims
  • DHFR 1719 Druggable Genome

    Alternate Names:

    1719
    DIHYDROFOLATE REDUCTASE
    DHFR
    DHFRP1
    DYR
    126060
    2861
    ENSG00000228716
    OTTHUMG00000162529
    P00374
    DYR_HUMAN
    ENSG00000188985
    DIHYDROFOLATE REDUCTASE (EC 1.5.1.3). [SOURCE:UNIPROT/SWISSPROT;ACC:P00374]
    ENSG00000168129
    PA143
    T17345

    Gene Info:

    Uniprot Evidence 1: Evidence at protein level
    Interpro Short Name DHFR_dom
    Human Readable Name DRUGGABLE GENOME
    Interpro Type Domain
    Interpro Acc IPR001796
    Interpro Name Dihydrofolate reductase domain
    Uniprot Status Swiss-Prot
    Target Subclass 1.5.1.3
    Target Main Class Enzymes
    Target Class Enzymes
    Target Subclass EC:1.5.1.3
    Gene Biotype PROTEIN_CODING
    (10 More Sources)

    Gene Categories: Category Details

    DRUGGABLE GENOME
    ENZYME

    Publications:

    Shimanovsky et al., 2013, Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma., Expert Opin Pharmacother
    Fidock et al., 1997, Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil., Proc. Natl. Acad. Sci. U.S.A.
    Wooden et al., 1997, Analysis in yeast of antimalaria drugs that target the dihydrofolate reductase of Plasmodium falciparum., Mol. Biochem. Parasitol.
    Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
    Rastelli et al., 2003, Structure of Plasmodium vivax dihydrofolate reductase determined by homology modeling and molecular dynamics refinement., Bioorg. Med. Chem. Lett.
    Tropak MB et al., 2015, Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-N-acetylhexosaminidase Activity., J Med Chem
    Pivot et al., 2001, Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck., Br. J. Cancer
    Kindler, 2002, Pemetrexed in pancreatic cancer., Semin. Oncol.
    Hanauske et al., 2001, Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors., Oncologist
    Mauritz et al., 2002, Multiple mechanisms of resistance to methotrexate and novel antifolates in human CCRF-CEM leukemia cells and their implications for folate homeostasis., Biochem. Pharmacol.
    Adjei, 2001, Gemcitabine and Pemetrexed disodium in treating breast cancer., Oncology (Williston Park, N.Y.)
    Adjei, 2002, Pemetrexed in the treatment of selected solid tumors., Semin. Oncol.
    Giovannetti et al., 2005, Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human non-small-cell lung cancer cells., Mol. Pharmacol.
    Norman, 2001, Pemetrexed disodium (Eli Lilly)., Curr Opin Investig Drugs
    Schultz et al., Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75-1 human breast carcinoma cells., Anticancer Res.
    Molina et al., 2003, The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy., Clin Lung Cancer
    Adjei, 2001, Gemcitabine and pemetrexed disodium combinations in vitro and in vivo., Lung Cancer
    Corrigan A et al., 2014, Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway analysis reveals novel toxicity associations., Pharmacogenomics J
    Jung M et al., 2013, Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung., Yonsei Med J
    Kodidela S et al., 2015, Influence of dihydrofolate reductase gene polymorphisms rs408626 (-317A>G) and rs442767 (-680C>A) on the outcome of methotrexate-based maintenance therapy in South Indian patients with acute lymphoblastic leukemia., Eur J Clin Pharmacol
    Jabeen S et al., 2015, Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate., Pharmacogenomics J
    Salazar J et al., 2014, Polymorphisms in genes involved in the mechanism of action of methotrexate: are they associated with outcome in rheumatoid arthritis patients?, Pharmacogenomics
    Salazar J et al., 2012, Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia., Pharmacogenomics J
    Sharma S et al., 2009, Purine biosynthetic pathway genes and methotrexate response in rheumatoid arthritis patients among north Indians., Pharmacogenet Genomics
    Al-Shakfa F et al., 2009, DNA variants in region for noncoding interfering transcript of dihydrofolate reductase gene and outcome in childhood acute lymphoblastic leukemia., Clin Cancer Res
    Ongaro A et al., 2009, Gene polymorphisms in folate metabolizing enzymes in adult acute lymphoblastic leukemia: effects on methotrexate-related toxicity and survival., Haematologica
    Neef et al., 1976, Interaction of 1,N6-ethenoadenine derivatives of triphosphopyridine and reduced triphosphopyridine nucleotides with dihydrofolate reductase from amethopterin-resistant L1210 cells., Biochemistry
    Hänggi et al., 1976, Altered regulation of the rate of synthesis of dihydrofolate reductase in methotrexate-resistant hamster cells., J. Biol. Chem.
    Wani et al., 1994, Increased methotrexate resistance and dhfr gene amplification as a consequence of induced Ha-ras expression in NIH 3T3 cells., Cancer Res.
    Kaufman et al., 1981, Amplification and loss of dihydrofolate reductase genes in a Chinese hamster ovary cell line., Mol. Cell. Biol.
    Domin et al., 1983, Establishment of dihydrofolate reductase-increased human cell lines and relationship between dihydrofolate reductase levels and gene copy., Cancer Res.
    Thompson et al., 1992, Assay for expression of methotrexate-resistant dihydrofolate reductase activity in the presence of drug-sensitive enzyme., J Pharmacol Toxicol Methods
    Selassie et al., 1982, A comparison of the inhibition of growth of methotrexate-resistant and -sensitive leukemia cells in culture by triazines. Evidence for a new mechanism of cell resistance to methotrexate., J. Med. Chem.
    Cavalcanti et al., 1992, Simultaneous changes in various mechanisms that mediate the cell incorporation of folate compounds account for low levels of resistance to methotrexate., Cell Biochem. Funct.
    Serra et al., 2004, Analysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells., Ann. Oncol.
    Bennett et al., 2006, Neutron diffraction studies of Escherichia coli dihydrofolate reductase complexed with methotrexate., Proc. Natl. Acad. Sci. U.S.A.
    Uga et al., 2006, A new mechanism of methotrexate action revealed by target screening with affinity beads., Mol. Pharmacol.
    Al-Rashood et al., 2006, Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs., Bioorg. Med. Chem.
    Totani et al., 2006, High-mannose-type glycan modifications of dihydrofolate reductase using glycan-methotrexate conjugates., Bioorg. Med. Chem.
    Assaraf, 2007, Molecular basis of antifolate resistance., Cancer Metastasis Rev.
    Inoue K et al., 2014, Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy., Drug Metab Pharmacokinet
    Nahimana et al., 2004, Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with failure of prophylaxis., Antimicrob. Agents Chemother.
    Floris-Moore et al., 2003, Adverse reactions to trimethoprim/sulfamethoxazole in AIDS., Ann Pharmacother
    Rosowsky et al., 2004, Synthesis of 2,4-diamino-6-[2'-O-(omega-carboxyalkyl)oxydibenz[b,f]azepin-5-yl]methylpteridines as potent and selective inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductase., J. Med. Chem.
    Barrow et al., 2004, Functional cloning of Bacillus anthracis dihydrofolate reductase and confirmation of natural resistance to trimethoprim., Antimicrob. Agents Chemother.
    Laskowska et al., 2003, Trimethoprim induces heat shock proteins and protein aggregation in E. coli cells., Curr. Microbiol.
    Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov
    Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov
    Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.
    Selhub et al., 1978, Inhibition of folate enzymes by sulfasalazine., J. Clin. Invest.
    Takebe et al., 2001, Generation of dual resistance to 4-hydroperoxycyclophosphamide and methotrexate by retroviral transfer of the human aldehyde dehydrogenase class 1 gene and a mutated dihydrofolate reductase gene., Mol. Ther.
    Levine et al., 1985, Effects of estrogen and tamoxifen on the regulation of dihydrofolate reductase gene expression in a human breast cancer cell line., Cancer Res.
    Takemura et al., 1996, Biological activity and intracellular metabolism of ZD1694 in human leukemia cell lines with different resistance mechanisms to antifolate drugs., Jpn. J. Cancer Res.
    Li et al., 1995, Antitumor activity of antifolate inhibitors of thymidylate and purine synthesis in human soft tissue sarcoma cell lines with intrinsic resistance to methotrexate., Clin. Cancer Res.
    Polshakov et al., 1999, Structure and dynamics in solution of the complex of Lactobacillus casei dihydrofolate reductase with the new lipophilic antifolate drug trimetrexate., Protein Sci.
    Warlick et al., 2002, In vivo selection of antifolate-resistant transgenic hematopoietic stem cells in a murine bone marrow transplant model., J. Pharmacol. Exp. Ther.
    Bertino et al., 1999, Use of variants of dihydrofolate reductase in gene transfer to produce resistance to methotrexate and trimetrexate., Prog Exp Tumor Res
    Graffner-Nordberg et al., 2001, Design, synthesis, computational prediction, and biological evaluation of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii., J. Med. Chem.
    Zhu et al., Severe folate restriction results in depletion of and alteration in the composition of the intracellular folate pool, moderate sensitization to methotrexate and trimetrexate, upregulation of endogenous DHFR activity, and overexpression of metallothionein II and folate receptor alpha that, upon folate repletion, confer drug resistance to CHL cells., J. Exp. Ther. Oncol.
    Sweeney et al., 2003, Trimetrexate inhibits progression of the murine 32Dp210 model of chronic myeloid leukemia in animals expressing drug-resistant dihydrofolate reductase., Cancer Res.
    Sowers R et al., 2011, Impairment of methotrexate transport is common in osteosarcoma tumor samples., Sarcoma
  • PIRITREXIM   DHFR

    Interaction Score: 16.49

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    17139284 17016423 10592235


    Sources:
    TTD

  • PRALATREXATE   DHFR

    Interaction Score: 6.87

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Trial Name PDX
    Novel drug target Established target
    Mechanism of Interaction Dihydrofolate reductase inhibitor

    PMIDs:
    23409799


    Sources:
    TdgClinicalTrial ClearityFoundationClinicalTrial ChemblInteractions TEND

  • PEMETREXED   DHFR

    Interaction Score: 5.3

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Trial Name Alimta
    Novel drug target Established target
    Trial Name -

    PMIDs:
    11531245 12571811 11524555 11841783 11252887 12023793 15795320 11752352 11763166 11848474 14596699 11742712 24732178 23709418


    Sources:
    TdgClinicalTrial ClearityFoundationClinicalTrial TEND PharmGKB

  • TRIMETREXATE   DHFR

    Interaction Score: 4.58

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Trial Name -
    Novel drug target Established target

    PMIDs:
    10091649 11752096 10386066 11448221 12416030 12649191 11752352 21234348


    Sources:
    TdgClinicalTrial TEND

  • ICLAPRIM   DHFR

    Interaction Score: 4.12

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:

    PMIDs:
    None found


    Sources:
    TTD

  • CHEMBL22148   DHFR

    Interaction Score: 4.12

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    25984755


    Sources:
    DTC

  • METHOTREXATE SODIUM   DHFR

    Interaction Score: 4.12

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Dihydrofolate reductase inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • TRIMETHOPRIM   DHFR

    Interaction Score: 2.62

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:

    PMIDs:
    15504856 14632594 15115391 11752352 15561838 14629008


    Sources:
    TTD

  • PYRIMETHAMINE   DHFR

    Interaction Score: 2.47

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:

    PMIDs:
    9380737 9108546 11752352 12951104 25984755


    Sources:
    DTC

  • RALTITREXED   DHFR

    Interaction Score: 1.77

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    8698629 9816025


    Sources:
    NCI

  • TALOTREXIN   DHFR

    Interaction Score: 1.37

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    Trial Name talotrexin, PT-523,Talvesta
    Novel drug target Established target

    PMIDs:
    None found


    Sources:
    TdgClinicalTrial

  • PERFOSFAMIDE   DHFR

    Interaction Score: 1.37

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    11162315


    Sources:
    NCI

  • METHOTREXATE   DHFR

    Interaction Score: 1.03

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Novel drug target Established target
    Trial Name VIBEX MTX
    Mechanism of Interaction Dihydrofolate reductase inhibitor

    PMIDs:
    26335211 25778468 25084201 21747412 19902562 19861437 19648163 9129 944698 8162600 7346712 6831441 1489988 7057421 1533575 14679136 17130456 16936229 16971132 16647263 11752352 17333344 24284432


    Sources:
    TdgClinicalTrial ChemblInteractions NCI PharmGKB

  • SULFASALAZINE   DHFR

    Interaction Score: 0.36

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    22555


    Sources:
    NCI

  • TAMOXIFEN   DHFR

    Interaction Score: 0.14

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    3978632


    Sources:
    NCI

  • Ensembl: ENSG00000228716

    • Version: 101_38

    Alternate Names:
    DHFR Ensembl Gene Name

    Gene Info:
    Gene Biotype PROTEIN_CODING

    Publications:

  • HopkinsGroom: P00374

    • Version: 11-September-2012

    Alternate Names:
    DHFR Uniprot Gene Name
    ENSG00000228716 Ensembl Gene Id
    DYR_HUMAN Uniprot Id

    Gene Info:
    Uniprot Evidence 1: Evidence at protein level
    Interpro Short Name DHFR_dom
    Human Readable Name DRUGGABLE GENOME

    Gene Categories:
    DRUGGABLE GENOME

    Publications:

  • TEND: P00374

    • Version: 01-August-2011

    Alternate Names:
    ENSG00000228716 Ensembl Gene Id
    P00374 Uniprot Accession
    DHFR Gene Symbol

    Gene Info:
    Target Subclass 1.5.1.3
    Target Main Class Enzymes

    Publications:

  • RussLampel: ENSG00000188985

    • Version: 26-July-2011

    Alternate Names:
    DHFR Display Id
    ENSG00000188985 Ensembl Gene Id
    DIHYDROFOLATE REDUCTASE (EC 1.5.1.3). [SOURCE:UNIPROT/SWISSPROT;ACC:P00374] Description

    Gene Info:
    Human Readable Name DRUGGABLE GENOME

    Gene Categories:
    DRUGGABLE GENOME

    Publications:

  • TdgClinicalTrial: P00374

    • Version: January-2014

    Alternate Names:
    DHFR Gene Symbol

    Gene Info:
    Target Class Enzymes
    Target Subclass EC:1.5.1.3

    Publications:

  • RussLampel: ENSG00000168129

    • Version: 26-July-2011

    Alternate Names:
    DHFR Display Id
    DIHYDROFOLATE REDUCTASE (EC 1.5.1.3). [SOURCE:UNIPROT/SWISSPROT;ACC:P00374] Description
    ENSG00000168129 Ensembl Gene Id

    Gene Info:
    Human Readable Name DRUGGABLE GENOME

    Gene Categories:
    DRUGGABLE GENOME

    Publications:

  • PharmGKB: DHFR

    • Version: 18-August-2020

    Alternate Names:
    PA143 PharmGKB ID

    Gene Info:

    Publications:
    Corrigan A et al., 2014, Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway analysis reveals novel toxicity associations., Pharmacogenomics J
    Jung M et al., 2013, Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung., Yonsei Med J
    Salazar J et al., 2014, Polymorphisms in genes involved in the mechanism of action of methotrexate: are they associated with outcome in rheumatoid arthritis patients?, Pharmacogenomics

  • NCI: DHFR

    • Version: 14-September-2017

    Alternate Names:

    Gene Info:

    Publications:
    Li et al., 1995, Antitumor activity of antifolate inhibitors of thymidylate and purine synthesis in human soft tissue sarcoma cell lines with intrinsic resistance to methotrexate., Clin. Cancer Res.
    Schornagel et al., 1984, Synthesis and evaluation of 2,4-diaminoquinazoline antifolates with activity against methotrexate-resistant human tumor cells., Biochem. Pharmacol.
    Tang et al., 1994, Formation and repair of antitumor antibiotic CC-1065-induced DNA adducts in the adenine phosphoribosyltransferase and amplified dihydrofolate reductase genes of Chinese hamster ovary cells., Biochemistry

  • DTC: DHFR

    • Version: 02-September-2020

    Alternate Names:

    Gene Info:

    Publications:
    Tropak MB et al., 2015, Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-N-acetylhexosaminidase Activity., J Med Chem

  • ChemblInteractions: DHFR

    • Version: chembl_23

    Alternate Names:
    DHFR GENE_SYMBOL
    Dihydrofolate reductase UNIPROT

    Gene Info:

    Publications:

  • HingoraniCasas: ENSG00000228716

    • Version: 31-May-2017

    Alternate Names:
    ENSG00000228716 Gene Symbol
    DHFR Ensembl Id

    Gene Info:

    Gene Categories:
    DRUGGABLE GENOME

    Publications:

  • TTD: Dihydrofolate reductase

    • Version: 2020.06.01

    Alternate Names:
    DHFR TTD Gene Abbreviation
    T17345 TTD Target ID

    Gene Info:

    Publications:

  • Pharos: DHFR

    • Version: 01-February-2022

    Alternate Names:
    Dihydrofolate reductase Gene Name
    P00374 UniProt ID

    Gene Info:

    Gene Categories:
    ENZYME

    Publications:

  • ClearityFoundationClinicalTrial: DHFR

    • Version: 15-June-2013

    Alternate Names:

    Gene Info:

    Publications:

Disclaimer: This resource is intended for purely research purposes. It should not be used for emergencies or medical or professional advice.

A finding of a drug-gene interaction or potentially druggable category does not necessarily indicate effectiveness (or lack thereof) of any drug or treatment regimen. A finding of no interaction or no potentially druggable category does not necessarily indicate lack of effectiveness of any drug or treatment regimen. Drug-gene interactions or potentially druggable categories are not presented in ranked order of potential or predicted efficacy.

The dgidb.org website does not provide any medical or healthcare products, services or advice, and is not for medical emergencies or urgent situations. IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY, CALL YOUR DOCTOR OR 911 IMMEDIATELY. Information contained on this website is not a substitute for a doctor's medical judgment or advice. We recommend that you discuss your specific, individual health concerns with your doctor or health care professional.

DGIdb (v4.2.0 - sha1 afd9f30b) • Last updated 2020-10-21