Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T75890
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| Former ID |
TTDR01187
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| Target Name |
Dihydropyrimidine dehydrogenase [NADP+]
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| Gene Name |
DPYD
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| Synonyms |
DHPDHase; DPD; Dihydropyrimidine dehydrogenase; Dihydrothymine dehydrogenase; Dihydrouracil dehydrogenase; DPYD
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| Target Type |
Clinical Trial
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| Disease | Cancer [ICD9: 140-229; ICD10: C00-C96] | ||||
| Hyperlipidaemia [ICD9: 272.0-272.4; ICD10: E78] | |||||
| Unspecified [ICD code not available] | |||||
| Function |
Involved in pyrimidine base degradation and catalyzes the reduction of uracil and thymine. also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
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| BioChemical Class |
Dihydropyrimidine dehydrogenase
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| UniProt ID | |||||
| EC Number |
EC 1.3.1.2
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| Sequence |
MAPVLSKDSADIESILALNPRTQTHATLCSTSAKKLDKKHWKRNPDKNCFNCEKLENNFD
DIKHTTLGERGALREAMRCLKCADAPCQKSCPTNLDIKSFITSIANKNYYGAAKMIFSDN PLGLTCGMVCPTSDLCVGGCNLYATEEGPINIGGLQQFATEVFKAMSIPQIRNPSLPPPE KMSEAYSAKIALFGAGPASISCASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDV VNFEIELMKDLGVKIICGKSLSVNEMTLSTLKEKGYKAAFIGIGLPEPNKDAIFQGLTQD QGFYTSKDFLPLVAKGSKAGMCACHSPLPSIRGVVIVLGAGDTAFDCATSALRCGARRVF IVFRKGFVNIRAVPEEMELAKEEKCEFLPFLSPRKVIVKGGRIVAMQFVRTEQDETGKWN EDEDQMVHLKADVVISAFGSVLSDPKVKEALSPIKFNRWGLPEVDPETMQTSEAWVFAGG DVVGLANTTVESVNDGKQASWYIHKYVQSQYGASVSAKPELPLFYTPIDLVDISVEMAGL KFINPFGLASATPATSTSMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIIRGTTSGPMY GPGQSSFLNIELISEKTAAYWCQSVTELKADFPDNIVIASIMCSYNKNDWTELAKKSEDS GADALELNLSCPHGMGERGMGLACGQDPELVRNICRWVRQAVQIPFFAKLTPNVTDIVSI ARAAKEGGANGVTATNTVSGLMGLKSDGTPWPAVGIAKRTTYGGVSGTAIRPIALRAVTS IARALPGFPILATGGIDSAESGLQFLHSGASVLQVCSAIQNQDFTVIEDYCTGLKALLYL KSIEELQDWDGQSPATVSHQKGKPVPRIAELMDKKLPSFGPYLEQRKKIIAENKIRLKEQ NVAFSPLKRNCFIPKRPIPTIKDVIGKALQYLGTFGELSNVEQVVAMIDEEMCINCGKCY MTCNDSGYQAIQFDPETHLPTITDTCTGCTLCLSVCPIVDCIKMVSRTTPYEPKRGVPLS VNPVC |
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| Drugs and Mode of Action | |||||
| Drug(s) | Eniluracil | Drug Info | Phase 2 | Hyperlipidaemia | [1] |
| RO-09-4889 | Drug Info | Phase 1 | Cancer | [2] | |
| FL-386 | Drug Info | Discontinued in Phase 2 | Hyperlipidaemia | [3] | |
| Inhibitor | (5s)-5-Iododihydro-2,4(1h,3h)-Pyrimidinedione | Drug Info | [4] | ||
| 5-Fluorouracil | Drug Info | [5] | |||
| 5-Iodouracil | Drug Info | [4] | |||
| 6-Carboxymethyluracil | Drug Info | [4] | |||
| Flavin-Adenine Dinucleotide | Drug Info | [4] | |||
| Modulator | Eniluracil | Drug Info | [1] | ||
| FL-386 | Drug Info | [6], [7] | |||
| RO-09-4889 | Drug Info | [2], [6] | |||
| Uracil | Drug Info | [8] | |||
| Pathways | |||||
| BioCyc Pathway | Pyrimidine ribonucleosides degradation | ||||
| Thymine degradation | |||||
| Uracil degradation | |||||
| KEGG Pathway | Pyrimidine metabolism | ||||
| beta-Alanine metabolism | |||||
| Pantothenate and CoA biosynthesis | |||||
| Drug metabolism - other enzymes | |||||
| Metabolic pathways | |||||
| PANTHER Pathway | Pyrimidine Metabolism | ||||
| PathWhiz Pathway | Beta-Alanine Metabolism | ||||
| Pyrimidine Metabolism | |||||
| WikiPathways | Metabolism of nucleotides | ||||
| Fluoropyrimidine Activity | |||||
| References | |||||
| REF 1 | Eniluracil: an irreversible inhibitor of dihydropyrimidine dehydrogenase. Expert Opin Investig Drugs. 2000 Jul;9(7):1635-49. | ||||
| REF 2 | Single ascending dose tolerability, pharmacokinetic-pharmacodynamic study of dihydropyrimidine dehydrogenase inhibitor Ro 09-4889. Clin Cancer Res. 2004 Apr 1;10(7):2327-35. | ||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002285) | ||||
| REF 4 | How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||
| REF 5 | Enhancement of the antitumour activity of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase activity (DPD) using 5-chloro-2,4-dihydroxypyridine (CDHP) in human tumour cells. Eur J Cancer. 2002 Jun;38(9):1271-7. | ||||
| REF 6 | Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36. | ||||
| REF 7 | Effects of FL-386 on faecal lipid excretion in humans. J Int Med Res. 1993 Sep-Oct;21(5):225-33. | ||||
| REF 8 | The ChEMBL database in 2017. | ||||
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