Target Information

Target General Infomation
Target ID
T75890
Former ID
TTDR01187
Target Name
Dihydropyrimidine dehydrogenase [NADP+]
Gene Name
DPYD
Synonyms
DHPDHase; DPD; Dihydropyrimidine dehydrogenase; Dihydrothymine dehydrogenase; Dihydrouracil dehydrogenase; DPYD
Target Type
Clinical Trial
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.
BioChemical Class
Dihydropyrimidine dehydrogenase
UniProt ID
Q12882
EC Number
EC 1.3.1.2
Sequence
MAPVLSKDSADIESILALNPRTQTHATLCSTSAKKLDKKHWKRNPDKNCFNCEKLENNFD
DIKHTTLGERGALREAMRCLKCADAPCQKSCPTNLDIKSFITSIANKNYYGAAKMIFSDN
PLGLTCGMVCPTSDLCVGGCNLYATEEGPINIGGLQQFATEVFKAMSIPQIRNPSLPPPE
KMSEAYSAKIALFGAGPASISCASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDV
VNFEIELMKDLGVKIICGKSLSVNEMTLSTLKEKGYKAAFIGIGLPEPNKDAIFQGLTQD
QGFYTSKDFLPLVAKGSKAGMCACHSPLPSIRGVVIVLGAGDTAFDCATSALRCGARRVF
IVFRKGFVNIRAVPEEMELAKEEKCEFLPFLSPRKVIVKGGRIVAMQFVRTEQDETGKWN
EDEDQMVHLKADVVISAFGSVLSDPKVKEALSPIKFNRWGLPEVDPETMQTSEAWVFAGG
DVVGLANTTVESVNDGKQASWYIHKYVQSQYGASVSAKPELPLFYTPIDLVDISVEMAGL
KFINPFGLASATPATSTSMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIIRGTTSGPMY
GPGQSSFLNIELISEKTAAYWCQSVTELKADFPDNIVIASIMCSYNKNDWTELAKKSEDS
GADALELNLSCPHGMGERGMGLACGQDPELVRNICRWVRQAVQIPFFAKLTPNVTDIVSI
ARAAKEGGANGVTATNTVSGLMGLKSDGTPWPAVGIAKRTTYGGVSGTAIRPIALRAVTS
IARALPGFPILATGGIDSAESGLQFLHSGASVLQVCSAIQNQDFTVIEDYCTGLKALLYL
KSIEELQDWDGQSPATVSHQKGKPVPRIAELMDKKLPSFGPYLEQRKKIIAENKIRLKEQ
NVAFSPLKRNCFIPKRPIPTIKDVIGKALQYLGTFGELSNVEQVVAMIDEEMCINCGKCY
MTCNDSGYQAIQFDPETHLPTITDTCTGCTLCLSVCPIVDCIKMVSRTTPYEPKRGVPLS
VNPVC
Drugs and Mode of Action
Drug(s) Eniluracil Drug Info Phase 2 Hyperlipidaemia [525898]
RO-09-4889 Drug Info Phase 1 Cancer [527031]
FL-386 Drug Info Discontinued in Phase 2 Hyperlipidaemia [545143]
Inhibitor (5s)-5-Iododihydro-2,4(1h,3h)-Pyrimidinedione Drug Info [551393]
5-Fluorouracil Drug Info [535468]
5-Iodouracil Drug Info [551393]
6-Carboxymethyluracil Drug Info [551393]
Flavin-Adenine Dinucleotide Drug Info [551393]
Modulator Eniluracil Drug Info [525898]
FL-386 Drug Info [531635], [533903]
RO-09-4889 Drug Info [527031], [531635]
Uracil Drug Info [1572605]
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 525898Eniluracil: an irreversible inhibitor of dihydropyrimidine dehydrogenase. Expert Opin Investig Drugs. 2000 Jul;9(7):1635-49.
Ref 527031Single ascending dose tolerability, pharmacokinetic-pharmacodynamic study of dihydropyrimidine dehydrogenase inhibitor Ro 09-4889. Clin Cancer Res. 2004 Apr 1;10(7):2327-35.
Ref 545143Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002285)
Ref 525898Eniluracil: an irreversible inhibitor of dihydropyrimidine dehydrogenase. Expert Opin Investig Drugs. 2000 Jul;9(7):1635-49.
Ref 527031Single ascending dose tolerability, pharmacokinetic-pharmacodynamic study of dihydropyrimidine dehydrogenase inhibitor Ro 09-4889. Clin Cancer Res. 2004 Apr 1;10(7):2327-35.
Ref 531635Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
Ref 533903Effects of FL-386 on faecal lipid excretion in humans. J Int Med Res. 1993 Sep-Oct;21(5):225-33.
Ref 535468Enhancement 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 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 1572605The ChEMBL database in 2017.

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