Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T07137
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| Former ID |
TTDS00314
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| Target Name |
4-hydroxyphenylpyruvate dioxygenase
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| Gene Name |
HPD
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| Synonyms |
4HPPD; F Alloantigen; F protein; HPPDase; HPD
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| Target Type |
Successful
|
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| Disease | Hereditary tyrosinemia type 1 [ICD9: 270.2; ICD10: E70.2] | ||||
| Respiratory syncytial virus infection [ICD9: 79.6; ICD10: B97.4] | |||||
| Function |
Key enzyme in the degradation of tyrosine.
|
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| BioChemical Class |
Oxidoreductases acting on single donors
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| Target Validation |
T07137
|
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| UniProt ID | |||||
| EC Number |
EC 1.13.11.27
|
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| Sequence |
MTTYSDKGAKPERGRFLHFHSVTFWVGNAKQAASFYCSKMGFEPLAYRGLETGSREVVSH
VIKQGKIVFVLSSALNPWNKEMGDHLVKHGDGVKDIAFEVEDCDYIVQKARERGAKIMRE PWVEQDKFGKVKFAVLQTYGDTTHTLVEKMNYIGQFLPGYEAPAFMDPLLPKLPKCSLEM IDHIVGNQPDQEMVSASEWYLKNLQFHRFWSVDDTQVHTEYSSLRSIVVANYEESIKMPI NEPAPGKKKSQIQEYVDYNGGAGVQHIALKTEDIITAIRHLRERGLEFLSVPSTYYKQLR EKLKTAKIKVKENIDALEELKILVDYDEKGYLLQIFTKPVQDRPTLFLEVIQRHNHQGFG AGNFNSLFKAFEEEQNLRGNLTNMETNGVVPGM |
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| Drugs and Mode of Action | |||||
| Drug(s) | Nitisinone | Drug Info | Approved | Hereditary tyrosinemia type 1 | [1], [2] |
| BMS-433771 | Drug Info | Terminated | Respiratory syncytial virus infection | [3] | |
| Inhibitor | (4-Hydroxy-phenoxy)-acetic acid | Drug Info | [4] | ||
| 2-(2-Bromo-benzoyl)-cyclohexane-1,3-dione | Drug Info | [5] | |||
| 2-(2-Chloro-benzoyl)-cyclohexane-1,3-dione | Drug Info | [5] | |||
| 2-(2-Iodo-benzoyl)-cyclohexane-1,3-dione | Drug Info | [5] | |||
| 2-(2-Methoxy-benzoyl)-cyclohexane-1,3-dione | Drug Info | [5] | |||
| 2-(2-Methyl-benzoyl)-cyclohexane-1,3-dione | Drug Info | [5] | |||
| 2-(2-Nitro-benzoyl)-cyclohexane-1,3-dione | Drug Info | [5] | |||
| 2-acetyl-3-hydroxycyclohex-2-enone | Drug Info | [6] | |||
| 2-Acetyl-cyclohexane-1,3-dione | Drug Info | [5] | |||
| 2-Cyclopropanecarbonyl-cyclohexane-1,3-dione | Drug Info | [5] | |||
| 2-Propionyl-cyclohexane-1,3-dione | Drug Info | [5] | |||
| 3-hydroxy-2-propionylcyclohex-2-enone | Drug Info | [6] | |||
| 3-Hydroxy-4-phenyl-5H-furan-2-one | Drug Info | [4] | |||
| Acetate Ion | Drug Info | [7] | |||
| BMS-433771 | Drug Info | [3] | |||
| Diketonitrile | Drug Info | [8] | |||
| Nitisinone | Drug Info | [8], [9] | |||
| Pathways | |||||
| KEGG Pathway | Ubiquinone and other terpenoid-quinone biosynthesis | ||||
| Tyrosine metabolism | |||||
| Phenylalanine metabolism | |||||
| Metabolic pathways | |||||
| References | |||||
| REF 1 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021232. | ||||
| REF 2 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6834). | ||||
| REF 3 | Emerging drugs for respiratory syncytial virus infection. Expert Opin Emerg Drugs. 2009 Jun;14(2):207-17. | ||||
| REF 4 | Bioorg Med Chem Lett. 2002 Jul 8;12(13):1709-13.Design, synthesis, and evaluation of postulated transient intermediate and substrate analogues as inhibitors of 4-hydroxyphenylpyruvate dioxygenase. | ||||
| REF 5 | Bioorg Med Chem Lett. 2000 May 1;10(9):843-5.SAR studies of 2-o-substituted-benzoyl- and 2-alkanoyl-cyclohexane-1,3-diones as inhibitors of 4-hydroxyphenylpyruvate dioxygenase. | ||||
| REF 6 | Bioorg Med Chem Lett. 2006 Dec 1;16(23):6024-7. Epub 2006 Sep 18.Enzyme inhibition potency enhancement by active site metal chelating and hydrogen bonding induced conformation-restricted cyclopropanecarbonyl derivatives. | ||||
| REF 7 | How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||
| REF 8 | 4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target. Drug News Perspect. 2003 Oct;16(8):493-6. | ||||
| REF 9 | Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. Expert Opin Pharmacother. 2008 May;9(7):1229-36. | ||||
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