Target Information

Target General Infomation
Target ID
T07137
Former ID
TTDS00314
Target Name
4-hydroxyphenylpyruvate dioxygenase
Gene Name
HPD
Synonyms
4HPPD; F Alloantigen; F protein; HPPDase; HPD
Target Type
Successful
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.
BioChemical Class
Oxidoreductases acting on single donors
Target Validation
T07137
UniProt ID
P32754
EC Number
EC 1.13.11.27
Sequence
MTTYSDKGAKPERGRFLHFHSVTFWVGNAKQAASFYCSKMGFEPLAYRGLETGSREVVSH
VIKQGKIVFVLSSALNPWNKEMGDHLVKHGDGVKDIAFEVEDCDYIVQKARERGAKIMRE
PWVEQDKFGKVKFAVLQTYGDTTHTLVEKMNYIGQFLPGYEAPAFMDPLLPKLPKCSLEM
IDHIVGNQPDQEMVSASEWYLKNLQFHRFWSVDDTQVHTEYSSLRSIVVANYEESIKMPI
NEPAPGKKKSQIQEYVDYNGGAGVQHIALKTEDIITAIRHLRERGLEFLSVPSTYYKQLR
EKLKTAKIKVKENIDALEELKILVDYDEKGYLLQIFTKPVQDRPTLFLEVIQRHNHQGFG
AGNFNSLFKAFEEEQNLRGNLTNMETNGVVPGM
Drugs and Mode of Action
Drug(s) Nitisinone Drug Info Approved Hereditary tyrosinemia type 1 [538562], [541915]
BMS-433771 Drug Info Terminated Respiratory syncytial virus infection [537350]
Inhibitor (4-Hydroxy-phenoxy)-acetic acid Drug Info [526361]
2-(2-Bromo-benzoyl)-cyclohexane-1,3-dione Drug Info [525791]
2-(2-Chloro-benzoyl)-cyclohexane-1,3-dione Drug Info [525791]
2-(2-Iodo-benzoyl)-cyclohexane-1,3-dione Drug Info [525791]
2-(2-Methoxy-benzoyl)-cyclohexane-1,3-dione Drug Info [525791]
2-(2-Methyl-benzoyl)-cyclohexane-1,3-dione Drug Info [525791]
2-(2-Nitro-benzoyl)-cyclohexane-1,3-dione Drug Info [525791]
2-acetyl-3-hydroxycyclohex-2-enone Drug Info [528436]
2-Acetyl-cyclohexane-1,3-dione Drug Info [525791]
2-Cyclopropanecarbonyl-cyclohexane-1,3-dione Drug Info [525791]
2-Propionyl-cyclohexane-1,3-dione Drug Info [525791]
3-hydroxy-2-propionylcyclohex-2-enone Drug Info [528436]
3-Hydroxy-4-phenyl-5H-furan-2-one Drug Info [526361]
Acetate Ion Drug Info [551393]
BMS-433771 Drug Info [537350]
Diketonitrile Drug Info [535880]
Nitisinone Drug Info [535880], [536692]
Pathways
KEGG Pathway Ubiquinone and other terpenoid-quinone biosynthesis
Tyrosine metabolism
Phenylalanine metabolism
Metabolic pathways
References
Ref 537350Emerging drugs for respiratory syncytial virus infection. Expert Opin Emerg Drugs. 2009 Jun;14(2):207-17.
Ref 538562FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021232.
Ref 541915(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 525791Bioorg 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 526361Bioorg 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 528436Bioorg 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 5358804-Hydroxyphenylpyruvate dioxygenase as a drug discovery target. Drug News Perspect. 2003 Oct;16(8):493-6.
Ref 536692Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. Expert Opin Pharmacother. 2008 May;9(7):1229-36.
Ref 537350Emerging drugs for respiratory syncytial virus infection. Expert Opin Emerg Drugs. 2009 Jun;14(2):207-17.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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