Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE4HCYL)

DME Name Thymidine phosphorylase (TYMP)
Synonyms Platelet-derived endothelial cell growth factor; Gliostatin; TdRPase; PD-ECGF; ECGF1; TP; TYMP
Gene Name TYMP
UniProt ID
TYPH_HUMAN
INTEDE ID
DME0092
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
1890
EC Number EC: 2.4.2.4
Transferase
Glycosyltransferases
Pentosyltransferase
EC: 2.4.2.4
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MAALMTPGTGAPPAPGDFSGEGSQGLPDPSPEPKQLPELIRMKRDGGRLSEADIRGFVAA
VVNGSAQGAQIGAMLMAIRLRGMDLEETSVLTQALAQSGQQLEWPEAWRQQLVDKHSTGG
VGDKVSLVLAPALAACGCKVPMISGRGLGHTGGTLDKLESIPGFNVIQSPEQMQVLLDQA
GCCIVGQSEQLVPADGILYAARDVTATVDSLPLITASILSKKLVEGLSALVVDVKFGGAA
VFPNQEQARELAKTLVGVGASLGLRVAAALTAMDKPLGRCVGHALEVEEALLCMDGAGPP
DLRDLVTTLGGALLWLSGHAGTQAQGAARVAAALDDGSALGRFERMLAAQGVDPGLARAL
CSGSPAERRQLLPRAREQEELLAPADGTVELVRALPLALVLHELGAGRSRAGEPLRLGVG
AELLVDVGQRLRRGTPWLRVHRDGPALSGPQSRALQEALVLSDRAPFAAPSPFAELVLPP
QQ
Function This enzyme catalyzes the reversible phosphorolysis of thymidine.
KEGG Pathway
Bladder cancer (hsa05219 )
Drug metabolism - other enzymes (hsa00983 )
Metabolic pathways (hsa01100 )
Pyrimidine metabolism (hsa00240 )
Reactome Pathway
Pyrimidine salvage (R-HSA-73614 )
Pyrimidine catabolism (R-HSA-73621 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
4 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Capecitabine DMTS85L Colorectal cancer 2B91.Z Approved [9]
Floxuridine DM04LR2 Colorectal cancer 2B91.Z Approved [10]
Fluorouracil DMUM7HZ Solid tumour/cancer 2A00-2F9Z Approved [11]
Trifluridine DMG2YBD Virus infection 1A24-1D9Z Approved [12]
1 Investigative Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Deoxythymidine DMR90HY Discovery agent N.A. Investigative [13]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 4.30E-10 -7.40E-01 -1.08E+00
Alopecia ED70 Skin from scalp 1.62E-01 -1.42E-01 -2.66E-01
Alzheimer's disease 8A20 Entorhinal cortex 6.96E-05 1.43E-01 5.00E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 6.84E-02 -1.15E-01 -4.30E-01
Aortic stenosis BB70 Calcified aortic valve 4.07E-01 4.63E-01 7.90E-01
Apnea 7A40 Hyperplastic tonsil 3.64E-01 -1.07E-01 -1.59E-01
Arthropathy FA00-FA5Z Peripheral blood 3.65E-02 1.33E-01 3.98E-01
Asthma CA23 Nasal and bronchial airway 2.72E-01 -1.79E-01 -1.23E-01
Atopic dermatitis EA80 Skin 3.40E-14 2.00E+00 4.94E+00
Autism 6A02 Whole blood 1.49E-01 2.03E-01 3.87E-01
Autoimmune uveitis 9A96 Peripheral monocyte 7.68E-02 5.19E-01 2.03E+00
Autosomal dominant monocytopenia 4B04 Whole blood 2.11E-01 -1.44E-01 -2.93E-01
Bacterial infection of gingival 1C1H Gingival tissue 7.70E-02 8.71E-02 1.51E-01
Batten disease 5C56.1 Whole blood 7.72E-01 9.45E-02 1.89E-01
Behcet's disease 4A62 Peripheral blood 4.00E-01 2.83E-01 1.01E+00
Bipolar disorder 6A60-6A6Z Prefrontal cortex 8.76E-01 -4.24E-02 -3.14E-01
Bladder cancer 2C94 Bladder tissue 6.64E-10 1.77E+00 5.79E+00
Breast cancer 2C60-2C6Z Breast tissue 4.06E-96 1.03E+00 1.87E+00
Cardioembolic stroke 8B11.20 Whole blood 8.60E-01 -7.06E-02 -2.34E-01
Cervical cancer 2C77 Cervical tissue 7.88E-04 6.50E-01 1.08E+00
Childhood onset rheumatic disease FA20.Z Peripheral blood 9.60E-01 3.76E-01 3.12E-01
Chronic hepatitis C 1E51.1 Whole blood 7.68E-01 -4.18E-01 -3.86E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 3.81E-01 -1.75E-01 -2.72E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 9.72E-01 -2.99E-02 -6.38E-02
Chronic rhinosinusitis CA0A Sinus mucosa tissue 1.18E-01 3.01E-01 1.57E+00
Colon cancer 2B90 Colon tissue 1.53E-41 4.64E-01 1.26E+00
Coronary artery disease BA80-BA8Z Peripheral blood 3.31E-01 2.02E-01 7.04E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 2.95E-01 -3.06E-01 -5.31E-01
Endometriosis GA10 Endometrium tissue 5.15E-04 3.59E-01 1.13E+00
Familial hypercholesterolemia 5C80.00 Peripheral blood 1.73E-01 -1.68E-01 -5.29E-01
Familial hypercholesterolemia 5C80.00 Whole blood 7.28E-11 1.36E+00 2.37E+00
Gastric cancer 2B72 Gastric tissue 2.16E-01 9.78E-01 1.11E+00
Glioblastopma 2A00.00 Nervous tissue 5.94E-28 2.65E-01 6.31E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 4.56E-01 -9.03E-01 -1.09E+00
Glioma 2A00.0Y-2A00.0Z White matter tissue 9.73E-01 3.09E-02 4.46E-02
Head and neck cancer 2D42 Head and neck tissue 1.32E-38 1.42E+00 2.45E+00
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 1.05E-05 4.00E-01 1.73E+00
Huntington's disease 8A01.10 Whole blood 6.81E-01 1.95E-01 1.93E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 4.64E-01 1.37E-01 2.85E-01
Immunodeficiency 4A00-4A20 Peripheral blood 5.01E-07 1.07E+00 5.94E+00
Influenza 1E30 Whole blood 6.18E-01 -1.93E-01 -2.91E+00
Interstitial cystitis GC00.3 Bladder tissue 3.49E-06 1.29E+00 1.33E+01
Intracranial aneurysm 8B01.0 Intracranial artery 1.74E-04 1.84E+00 4.25E+00
Irritable bowel syndrome DD91.0 Rectal colon tissue 9.70E-01 -1.66E-02 -1.01E-01
Ischemic stroke 8B11 Peripheral blood 5.31E-01 -1.15E-01 -1.99E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 1.40E-01 -1.82E-01 -1.92E-01
Lateral sclerosis 8B60.4 Skin 1.12E-01 -1.33E-01 -1.04E+00
Lateral sclerosis 8B60.4 Cervical spinal cord 2.83E-01 -1.22E-01 -3.46E-01
Liver cancer 2C12.0 Liver tissue 4.78E-01 3.65E-02 8.13E-02
Liver failure DB99.7-DB99.8 Liver tissue 3.51E-02 6.02E-01 1.12E+00
Lung cancer 2C25 Lung tissue 1.33E-06 3.07E-01 5.19E-01
Lupus erythematosus 4A40 Whole blood 2.06E-02 -4.22E-02 -2.99E-02
Major depressive disorder 6A70-6A7Z Hippocampus 6.50E-01 -3.41E-02 -2.48E-01
Major depressive disorder 6A70-6A7Z Whole blood 7.91E-01 -2.57E-02 -5.70E-02
Melanoma 2C30 Skin 3.29E-06 1.05E+00 1.41E+00
Multiple myeloma 2A83.1 Peripheral blood 9.06E-01 -6.22E-02 -1.46E-01
Multiple myeloma 2A83.1 Bone marrow 2.46E-02 1.14E-01 4.82E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 5.62E-03 3.77E-01 1.37E+00
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 7.90E-03 1.96E-01 6.85E-01
Myelofibrosis 2A20.2 Whole blood 3.90E-02 -1.12E-01 -2.73E-01
Myocardial infarction BA41-BA50 Peripheral blood 1.01E-01 6.86E-01 4.54E-01
Myopathy 8C70.6 Muscle tissue 5.78E-05 5.24E-01 2.31E+00
Neonatal sepsis KA60 Whole blood 6.75E-04 5.49E-01 5.79E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 5.55E-03 -3.87E-01 -1.48E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 6.22E-01 5.68E-02 2.80E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 7.73E-01 1.16E-01 3.29E-01
Olive pollen allergy CA08.00 Peripheral blood 3.22E-01 -1.10E-01 -1.64E-01
Oral cancer 2B6E Oral tissue 1.23E-04 8.72E-01 1.08E+00
Osteoarthritis FA00-FA0Z Synovial tissue 2.80E-01 2.72E-01 3.74E-01
Osteoporosis FB83.1 Bone marrow 1.85E-01 -3.89E-01 -8.51E-01
Ovarian cancer 2C73 Ovarian tissue 2.69E-04 8.04E-01 1.82E+00
Pancreatic cancer 2C10 Pancreas 7.36E-03 6.71E-01 6.99E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 4.01E-01 1.64E-01 4.56E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 1.75E-05 1.42E+00 1.61E+00
Pituitary cancer 2D12 Pituitary tissue 1.05E-02 -5.55E-01 -1.14E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 3.31E-03 -7.10E-01 -1.38E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 4.77E-01 5.52E-02 2.91E-01
Polycythemia vera 2A20.4 Whole blood 5.03E-01 7.81E-02 1.85E-01
Pompe disease 5C51.3 Biceps muscle 9.91E-01 3.55E-02 3.60E-01
Preterm birth KA21.4Z Myometrium 1.21E-01 -1.52E-01 -2.16E-01
Prostate cancer 2C82 Prostate 1.21E-08 -9.45E-01 -2.30E+00
Psoriasis EA90 Skin 1.26E-19 5.76E-01 1.08E+00
Rectal cancer 2B92 Rectal colon tissue 6.05E-03 2.78E-01 1.39E+00
Renal cancer 2C90-2C91 Kidney 1.03E-06 1.38E+00 2.85E+00
Retinoblastoma 2D02.2 Uvea 6.10E-05 1.91E+00 1.38E+01
Rheumatoid arthritis FA20 Synovial tissue 1.06E-08 1.93E+00 6.42E+00
Rhinovirus infection CA42.1 Nasal epithelium tissue 8.61E-01 -7.87E-02 -2.03E-01
Schizophrenia 6A20 Prefrontal cortex 4.01E-02 2.82E-01 1.96E-01
Schizophrenia 6A20 Superior temporal cortex 4.91E-01 5.72E-02 3.20E-01
Scleroderma 4A42.Z Whole blood 9.38E-06 4.43E-01 2.04E+00
Seizure 8A60-8A6Z Whole blood 2.37E-01 6.59E-01 9.08E-01
Sensitive skin EK0Z Skin 1.99E-01 4.33E-01 1.55E+00
Sepsis with septic shock 1G41 Whole blood 2.60E-13 6.73E-01 7.92E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 2.52E-01 -3.92E-01 -1.44E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 5.50E-02 7.67E-02 4.45E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 4.27E-01 -1.15E-01 -5.90E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 9.72E-01 -5.51E-02 -1.60E-01
Skin cancer 2C30-2C3Z Skin 9.32E-10 4.50E-01 7.22E-01
Thrombocythemia 3B63 Whole blood 1.52E-01 -2.63E-02 -6.29E-02
Thrombocytopenia 3B64 Whole blood 4.56E-01 5.72E-01 6.56E-01
Thyroid cancer 2D10 Thyroid 7.90E-12 5.50E-01 8.68E-01
Tibial muscular dystrophy 8C75 Muscle tissue 1.98E-02 1.16E-01 6.15E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 6.59E-03 5.19E-01 4.08E+00
Type 2 diabetes 5A11 Liver tissue 4.68E-01 -8.98E-03 -1.71E-02
Ureter cancer 2C92 Urothelium 9.82E-01 1.49E-02 7.19E-02
Uterine cancer 2C78 Endometrium tissue 5.12E-02 3.14E-01 3.20E-01
Vitiligo ED63.0 Skin 9.56E-01 2.51E-02 9.03E-02
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⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name Thymidine phosphorylase (TYMP) DTT Info
DME DTT Type Successful
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Uridine DMQTREB Depression 6A70-6A7Z Approved [1]
23 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
1-(cyclohexyl)methyl-5'-O-tritylinosine DMS3XUC Discovery agent N.A. Investigative [2]
1-(cyclopropyl)methyl-5'-O-tritylinosine DMDU3X7 Discovery agent N.A. Investigative [2]
1-allyl-5'-O-tritylinosine DM2J5WH Discovery agent N.A. Investigative [2]
1-benzyl-5'-O-tritylinosine DMH0ZVR Discovery agent N.A. Investigative [2]
1-propyl-5'-O-tritylinosine DM5P01L Discovery agent N.A. Investigative [2]
2'-aminoimidazolylmethyluracils DMUJC2E Discovery agent N.A. Investigative [3]
5-benzyl-6-chloropyrimidine-2,4(1H,3H)-dione DMCKODQ Discovery agent N.A. Investigative [4]
5-bromo-6-(cyclopropylamino)uracil hydrochloride DMRY0OL Discovery agent N.A. Investigative [5]
5-bromo-6-hydrazinouracil hydrochloride DMZJE6M Discovery agent N.A. Investigative [5]
5-butyl-6-chloropyrimidine-2,4(1H,3H)-dione DMFKMYV Discovery agent N.A. Investigative [4]
5-chloro-6-hydrazinouracil hydrochloride DMMT7WO Discovery agent N.A. Investigative [5]
5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil DMEV0GO Discovery agent N.A. Investigative [6]
6-amino-5-bromouracil DM5SZHR Discovery agent N.A. Investigative [7]
6-amino-5-chlorouracil hydrochloride DMFPCSJ Discovery agent N.A. Investigative [5]
6-bromo-5-phenylpyrimidine-2,4(1H,3H)-dione DM8A1ZU Discovery agent N.A. Investigative [4]
6-chloro-5-(2-thienyl)pyrimidine-2,4(1H,3H)-dione DMSZML2 Discovery agent N.A. Investigative [4]
6-chloro-5-heptylpyrimidine-2,4(1H,3H)-dione DMASFR6 Discovery agent N.A. Investigative [4]
6-chloro-5-hexylpyrimidine-2,4(1H,3H)-dione DMP4V8Y Discovery agent N.A. Investigative [4]
6-chloro-5-pentylpyrimidine-2,4(1H,3H)-dione DMUJSP7 Discovery agent N.A. Investigative [4]
6-chloro-5-phenylpyrimidine-2,4(1H,3H)-dione DM90JMN Discovery agent N.A. Investigative [4]
6-chloro-5-propylpyrimidine-2,4(1H,3H)-dione DMB24LJ Discovery agent N.A. Investigative [4]
6-fluoro-5-phenylpyrimidine-2,4(1H,3H)-dione DM4Q5TX Discovery agent N.A. Investigative [4]
Thymine DMKGXB9 Discovery agent N.A. Investigative [8]
⏷ Show the Full List of 23 Investigative Drug(s)

References

1 Enzymatic activities of uridine and thymidine phosphorylase in normal and cancerous uterine cervical tissues. Hum Cell. 2007 Nov;20(4):107-10.
2 5'-O-tritylinosine and analogues as allosteric inhibitors of human thymidine phosphorylase. J Med Chem. 2006 Sep 7;49(18):5562-70.
3 Potential tumor-selective nitroimidazolylmethyluracil prodrug derivatives: inhibitors of the angiogenic enzyme thymidine phosphorylase. J Med Chem. 2003 Jan 16;46(2):207-9.
4 Discovery of 5-substituted-6-chlorouracils as efficient inhibitors of human thymidine phosphorylase. J Med Chem. 2007 Nov 29;50(24):6016-23.
5 Design and synthesis of novel 5,6-disubstituted uracil derivatives as potent inhibitors of thymidine phosphorylase. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1335-7.
6 The role of phosphate in the action of thymidine phosphorylase inhibitors: Implications for the catalytic mechanism. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1648-51.
7 Xanthine oxidase-activated prodrugs of thymidine phosphorylase inhibitors. Eur J Med Chem. 2008 Jun;43(6):1248-60.
8 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
9 Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45.
10 Enhanced cancer cell growth inhibition by dipeptide prodrugs of floxuridine: increased transporter affinity and metabolic stability. Mol Pharm. 2008 Sep-Oct;5(5):717-27.
11 5-Fluorouracil pharmacogenomics: still rocking after all these years? Pharmacogenomics. 2011 Feb;12(2):251-65.
12 Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9.
13 Thymidine catabolism as a metabolic strategy for cancer survival. Cell Rep. 2017 May 16;19(7):1313-1321.