DGIdb - DHFR Gene Record

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
BE0000330
2603
PA143
T17345
NM_000791
NP_000782

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
GuideToPharmacology Gene Category Name	1.-.-.- Oxidoreductases
GuideToPharmacology Gene Category ID	840
GuideToPharmacology Gene Category Name	Nucleoside synthesis and metabolism
GuideToPharmacology Gene Category ID	920

(12 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
Wooden et al., 1997, Analysis in yeast of antimalaria drugs that target the dihydrofolate reductase of Plasmodium falciparum., Mol. Biochem. Parasitol.
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
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
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.
Kindler, 2002, Pemetrexed in pancreatic cancer., 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.
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.
Hanauske et al., 2001, Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors., Oncologist
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
Adjei, 2002, Pemetrexed in the treatment of selected solid tumors., Semin. Oncol.
Molina et al., 2003, The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy., Clin Lung Cancer
Norman, 2001, Pemetrexed disodium (Eli Lilly)., Curr Opin Investig Drugs
Pivot et al., 2001, Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck., Br. J. Cancer
Schultz et al., Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75-1 human breast carcinoma cells., Anticancer Res.
Adjei, 2001, Gemcitabine and Pemetrexed disodium in treating breast cancer., Oncology (Williston Park, N.Y.)
Jung M et al., 2013, Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung., Yonsei Med J
Serra et al., 2004, Analysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells., Ann. Oncol.
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.
Domin et al., 1983, Establishment of dihydrofolate reductase-increased human cell lines and relationship between dihydrofolate reductase levels and gene copy., Cancer Res.
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.
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
Uga et al., 2006, A new mechanism of methotrexate action revealed by target screening with affinity beads., Mol. Pharmacol.
Ongaro A et al., 2009, Gene polymorphisms in folate metabolizing enzymes in adult acute lymphoblastic leukemia: effects on methotrexate-related toxicity and survival., Haematologica
Jabeen S et al., 2015, Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate., Pharmacogenomics J
Kaufman et al., 1981, Amplification and loss of dihydrofolate reductase genes in a Chinese hamster ovary cell line., Mol. Cell. Biol.
Sharma S et al., 2009, Purine biosynthetic pathway genes and methotrexate response in rheumatoid arthritis patients among north Indians., Pharmacogenet Genomics
Thompson et al., 1992, Assay for expression of methotrexate-resistant dihydrofolate reductase activity in the presence of drug-sensitive enzyme., J Pharmacol Toxicol Methods
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.
Totani et al., 2006, High-mannose-type glycan modifications of dihydrofolate reductase using glycan-methotrexate conjugates., Bioorg. Med. Chem.
Salazar J et al., 2012, Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia., Pharmacogenomics J
Assaraf, 2007, Molecular basis of antifolate resistance., Cancer Metastasis Rev.
Bennett et al., 2006, Neutron diffraction studies of Escherichia coli dihydrofolate reductase complexed with methotrexate., Proc. Natl. Acad. Sci. U.S.A.
Inoue K et al., 2014, Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy., Drug Metab Pharmacokinet
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.
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
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
Le Bras et al., 2003, The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum., Fundam Clin Pharmacol
Vasconcelos et al., Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase of isolates from the Amazon region of Brazil., Mem. Inst. Oswaldo Cruz
Durand et al., 2001, Plasmodium falciparum: pfcrt and DHFR mutations are associated with failure of chloroquine plus proguanil prophylaxis in travelers., J. Infect. Dis.
Tahar et al., 2001, Kinetic properties of dihydrofolate reductase from wild-type and mutant Plasmodium vivax expressed in Escherichia coli., Mol. Biochem. Parasitol.
Kaneko et al., 1999, Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil., J. Infect. Dis.
Barrow et al., 2004, Functional cloning of Bacillus anthracis dihydrofolate reductase and confirmation of natural resistance to trimethoprim., 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.
Nahimana et al., 2004, Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with failure of prophylaxis., Antimicrob. Agents Chemother.
Laskowska et al., 2003, Trimethoprim induces heat shock proteins and protein aggregation in E. coli cells., Curr. Microbiol.
Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.
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
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.
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.
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.
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.
Sowers R et al., 2011, Impairment of methotrexate transport is common in osteosarcoma tumor samples., Sarcoma
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.
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.
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.
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.
Bertino et al., 1999, Use of variants of dihydrofolate reductase in gene transfer to produce resistance to methotrexate and trimetrexate., Prog Exp Tumor Res
Al-Omary et al., 2010, Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones., Bioorg. Med. Chem.
Vickers et al., 2006, Biochemical and genetic analysis of methylenetetrahydrofolate reductase in Leishmania metabolism and virulence., J. Biol. Chem.
Argyrou et al., 2006, Proteome-wide profiling of isoniazid targets in Mycobacterium tuberculosis., Biochemistry

PIRITREXIM DHFR

Interaction Score: 8.88

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235 17139284 17016423

Sources:
TTD DrugBank
CHEMBL151958 DHFR

Interaction Score: 7.1

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235 17139284 17016423

Sources:
DrugBank
CHEMBL32113 DHFR

Interaction Score: 7.1

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235 17139284 17016423

Sources:
DrugBank
CHEMBL50514 DHFR

Interaction Score: 7.1

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235 17139284 17016423

Sources:
DrugBank
CHEMBL32190 DHFR

Interaction Score: 7.1

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235 17139284 17016423

Sources:
DrugBank
ICLAPRIM DHFR

Interaction Score: 5.33

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
TTD DrugBank GuideToPharmacology
CHEMBL576960 DHFR

Interaction Score: 3.55

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235

Sources:
DrugBank
CHEMBL573077 DHFR

Interaction Score: 3.55

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235

Sources:
DrugBank
CHEMBL459177 DHFR

Interaction Score: 3.55

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235

Sources:
DrugBank
CHEMBL485961 DHFR

Interaction Score: 3.55

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235

Sources:
DrugBank
CHEMBL301769 DHFR

Interaction Score: 3.55

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235

Sources:
DrugBank
CHEMBL325434 DHFR

Interaction Score: 3.55

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235

Sources:
DrugBank
CHEMBL575218 DHFR

Interaction Score: 3.55

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235

Sources:
DrugBank
CHEMBL36245 DHFR

Interaction Score: 3.55

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10592235

Sources:
DrugBank
PRALATREXATE DHFR

Interaction Score: 3.11

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name PDX

Novel drug target Established target

Mechanism of Interaction Dihydrofolate reductase inhibitor

PMIDs:
23409799

Sources:
ClearityFoundationClinicalTrial TEND TdgClinicalTrial DrugBank GuideToPharmacology ChemblInteractions
PEMETREXED DHFR

Interaction Score: 2.54

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

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

Sources:
ClearityFoundationClinicalTrial TEND PharmGKB TdgClinicalTrial DrugBank GuideToPharmacology
CHLOROGUANIDE DHFR

Interaction Score: 2.49

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
12667224 10998224 11740746 11295178 10068594 11752352

Sources:
DrugBank
TRIMETREXATE DHFR

Interaction Score: 2.37

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction <i>In vitro</i> inhibition of wild-type human DHFR

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
11752096 21234348 12416030 11448221 10091649 12649191 11752352 10386066

Sources:
TEND TdgClinicalTrial DrugBank GuideToPharmacology
METHOTREXATE SODIUM DHFR

Interaction Score: 1.78

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dihydrofolate reductase inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
CHEMBL22148 DHFR

Interaction Score: 1.18

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
25984755

Sources:
DTC
TRIMETHOPRIM DHFR

Interaction Score: 1.13

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
15561838 14632594 15115391 15504856 11752352 14629008

Sources:
TTD
PYRIMETHAMINE DHFR

Interaction Score: 1.04

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
9108546 12951104 25984755 11752352 9380737

Sources:
DTC DrugBank
RALTITREXED DHFR

Interaction Score: 0.67

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
9816025 8698629

Sources:
NCI
TALOTREXIN DHFR

Interaction Score: 0.59

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: 0.59

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11162315

Sources:
NCI
METHOTREXATE DHFR

Interaction Score: 0.48

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name VIBEX MTX

Specific Action of the Ligand Inhibition

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

Sources:
NCI PharmGKB TdgClinicalTrial DrugBank GuideToPharmacology ChemblInteractions
DIFLUNISAL DHFR

Interaction Score: 0.36

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Details of Interaction This is well below the peak plasma diflunisal levels reached at typical clinically administered doses.

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
SODIUM BETA-NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE DHFR

Interaction Score: 0.18

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17139284 17016423

Sources:
DrugBank
GENTAMICIN DHFR

Interaction Score: 0.15

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
20350811

Sources:
DrugBank
SULFASALAZINE DHFR

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22555

Sources:
NCI
TAMOXIFEN DHFR

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
3978632

Sources:
NCI
CHEMBL1161866 DHFR

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17032644 17115689

Sources:
DrugBank

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:
GuideToPharmacology: 1719
- Version: 29-September-2020
Alternate Names:

2861 HUGO Gene ID

2861 HUGO Gene Symbol

dihydrofolate reductase HUGO Gene Name

Gene Info:

GuideToPharmacology Gene Category Name 1.-.-.- Oxidoreductases

GuideToPharmacology Gene Category ID 840

GuideToPharmacology Gene Category Name Nucleoside synthesis and metabolism

Gene Categories:

ENZYME

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

DrugBank: BE0000330

Version: 5.1.7

Alternate Names:

DHFR DrugBank Gene Name

P00374 UniProt Accession

1719 Entrez Gene Id

Gene Info:

Publications:

Vickers et al., 2006, Biochemical and genetic analysis of methylenetetrahydrofolate reductase in Leishmania metabolism and virulence., J. Biol. Chem.

Argyrou et al., 2006, Proteome-wide profiling of isoniazid targets in Mycobacterium tuberculosis., Biochemistry

Wooden et al., 1997, Analysis in yeast of antimalaria drugs that target the dihydrofolate reductase of Plasmodium falciparum., Mol. Biochem. Parasitol.

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:
Pharos: DHFR
- Version: 03-September-2020
Alternate Names:

Dihydrofolate reductase Gene Name

P00374 UniProt ID

Gene Info:

Gene Categories:

ENZYME

Publications:
TTD: Dihydrofolate reductase
- Version: 2020.06.01
Alternate Names:

DHFR TTD Gene Abbreviation

T17345 TTD Target ID

Gene Info:

Publications:
ClearityFoundationClinicalTrial: DHFR
- Version: 15-June-2013
Alternate Names:

Gene Info:

Publications:

Specific Action of the Ligand	Inhibition
Endogenous Drug?	False
Direct Interaction?	False

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

Details of the Assay for Interaction	<i>In vitro</i> inhibition of wild-type human DHFR
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Mechanism of Interaction	Dihydrofolate reductase inhibitor
Direct Interaction	yes

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

Specific Action of the Ligand	Inhibition
Details of Interaction	This is well below the peak plasma diflunisal levels reached at typical clinically administered doses.
Endogenous Drug?	False

DHFR	Uniprot Gene Name
ENSG00000228716	Ensembl Gene Id
DYR_HUMAN	Uniprot Id

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

2861	HUGO Gene ID
2861	HUGO Gene Symbol
dihydrofolate reductase	HUGO Gene Name

DHFR	DrugBank Gene Name
P00374	UniProt Accession
1719	Entrez Gene Id

DHFR Gene Record

DHFR 1719 Druggable Genome

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235 17139284 17016423

Sources: TTD DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235 17139284 17016423

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235 17139284 17016423

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235 17139284 17016423

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235 17139284 17016423

Sources: DrugBank

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? False

PMIDs: None found

Sources: TTD DrugBank GuideToPharmacology

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10592235

Sources: DrugBank

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: 23409799

Sources: ClearityFoundationClinicalTrial TEND TdgClinicalTrial DrugBank GuideToPharmacology ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? True

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

Sources: ClearityFoundationClinicalTrial TEND PharmGKB TdgClinicalTrial DrugBank GuideToPharmacology

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info:

PMIDs: 12667224 10998224 11740746 11295178 10068594 11752352

Sources: DrugBank

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction <i>In vitro</i> inhibition of wild-type human DHFR Specific Action of the Ligand Inhibition Endogenous Drug? False

PMIDs: 11752096 21234348 12416030 11448221 10091649 12649191 11752352 10386066

Sources: TEND TdgClinicalTrial DrugBank GuideToPharmacology

Interaction Types & Directionality: inhibitor (inhibitory)

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

Interaction Types & Directionality:

n/a

PMIDs:
10592235 17139284 17016423

Sources:
TTD DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235 17139284 17016423

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235 17139284 17016423

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235 17139284 17016423

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235 17139284 17016423

Sources:
DrugBank

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
TTD DrugBank GuideToPharmacology

Interaction Types & Directionality:

n/a

PMIDs:
10592235

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
10592235

Sources:
DrugBank

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name PDX

Novel drug target Established target

Mechanism of Interaction Dihydrofolate reductase inhibitor

PMIDs:
23409799

Sources:
ClearityFoundationClinicalTrial TEND TdgClinicalTrial DrugBank GuideToPharmacology ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

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

Sources:
ClearityFoundationClinicalTrial TEND PharmGKB TdgClinicalTrial DrugBank GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
12667224 10998224 11740746 11295178 10068594 11752352

Sources:
DrugBank

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction <i>In vitro</i> inhibition of wild-type human DHFR

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
11752096 21234348 12416030 11448221 10091649 12649191 11752352 10386066

Sources:
TEND TdgClinicalTrial DrugBank GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dihydrofolate reductase inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

n/a

PMIDs:
25984755

Sources:
DTC

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
15561838 14632594 15115391 15504856 11752352 14629008

Sources:
TTD

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
9108546 12951104 25984755 11752352 9380737

Sources:
DTC DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
9816025 8698629

Sources:
NCI

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name talotrexin, PT-523,Talvesta

Novel drug target Established target

PMIDs:
None found

Sources:
TdgClinicalTrial

Interaction Types & Directionality:

n/a

PMIDs:
11162315