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.
Click to Show/Hide
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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 | |||||
|---|---|---|---|---|---|---|
| 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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