Target Information
Target General Information | Top | |||||
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Target ID |
T75890
(Former ID: TTDR01187)
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Target Name |
Dihydrothymine dehydrogenase (DPYD)
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Synonyms |
Dihydrouracil dehydrogenase; Dihydropyrimidine dehydrogenase [NADP(+)]; Dihydropyrimidine dehydrogenase; DPD; DHPDHase
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Gene Name |
DPYD
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil. Involved in pyrimidine base degradation.
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BioChemical Class |
CH/CH donor oxidoreductase
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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 Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
ADReCS ID | BADD_A01329 ; BADD_A01462 ; BADD_A02149 ; BADD_A03065 ; BADD_A04623 ; BADD_A05061 ; BADD_A06316 ; BADD_A06627 |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Fluorouracil | Drug Info | Approved | Solid tumour/cancer | [2] | |
Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | Eniluracil | Drug Info | Phase 2 | Hyperlipidaemia | [3] | |
2 | RO-09-4889 | Drug Info | Phase 1 | Solid tumour/cancer | [4] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | FL-386 | Drug Info | Discontinued in Phase 2 | Hyperlipidaemia | [5] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 5 Inhibitor drugs | + | ||||
1 | Fluorouracil | Drug Info | [1] | |||
2 | (5s)-5-Iododihydro-2,4(1h,3h)-Pyrimidinedione | Drug Info | [8] | |||
3 | 5-Iodouracil | Drug Info | [8] | |||
4 | 6-Carboxymethyluracil | Drug Info | [8] | |||
5 | Flavin-Adenine Dinucleotide | Drug Info | [8] | |||
Modulator | [+] 4 Modulator drugs | + | ||||
1 | Eniluracil | Drug Info | [3] | |||
2 | RO-09-4889 | Drug Info | [4], [6] | |||
3 | FL-386 | Drug Info | [6], [7] | |||
4 | Uracil | Drug Info | [9] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Affiliated Biological Pathways | Top | |||||
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BioCyc | [+] 3 BioCyc Pathways | + | ||||
1 | Pyrimidine ribonucleosides degradation | |||||
2 | Thymine degradation | |||||
3 | Uracil degradation | |||||
KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
1 | Pyrimidine metabolism | |||||
2 | beta-Alanine metabolism | |||||
3 | Pantothenate and CoA biosynthesis | |||||
4 | Drug metabolism - other enzymes | |||||
5 | Metabolic pathways | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Pyrimidine Metabolism | |||||
Pathwhiz Pathway | [+] 2 Pathwhiz Pathways | + | ||||
1 | Beta-Alanine Metabolism | |||||
2 | Pyrimidine Metabolism | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Metabolism of nucleotides | |||||
2 | Fluoropyrimidine Activity |
References | Top | |||||
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REF 1 | 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 2 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
REF 3 | Eniluracil: an irreversible inhibitor of dihydropyrimidine dehydrogenase. Expert Opin Investig Drugs. 2000 Jul;9(7):1635-49. | |||||
REF 4 | 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 5 | 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 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 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 9 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. |
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