Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8DSFC)

• DTT Name: Hydroxyphenylpyruvate dioxygenase (HPD)
• Synonyms: HPPDase; HPD; F Alloantigen; 4HPPD
• Gene Name: HPD
• DTT Type: Successful target; [1]
• BioChemical Class: Single donor oxidoreductase
• UniProt ID: HPPD_HUMAN
• TTD ID: T07137
• EC Number: EC 1.13.11.27
• Sequence:
  MTTYSDKGAKPERGRFLHFHSVTFWVGNAKQAASFYCSKMGFEPLAYRGLETGSREVVSH
  VIKQGKIVFVLSSALNPWNKEMGDHLVKHGDGVKDIAFEVEDCDYIVQKARERGAKIMRE
  PWVEQDKFGKVKFAVLQTYGDTTHTLVEKMNYIGQFLPGYEAPAFMDPLLPKLPKCSLEM
  IDHIVGNQPDQEMVSASEWYLKNLQFHRFWSVDDTQVHTEYSSLRSIVVANYEESIKMPI
  NEPAPGKKKSQIQEYVDYNGGAGVQHIALKTEDIITAIRHLRERGLEFLSVPSTYYKQLR
  EKLKTAKIKVKENIDALEELKILVDYDEKGYLLQIFTKPVQDRPTLFLEVIQRHNHQGFG
  AGNFNSLFKAFEEEQNLRGNLTNMETNGVVPGM
• Function: Key enzyme in the degradation of tyrosine.
• KEGG Pathway:
  Ubiquinone and other terpenoid-quinone biosynthesis (mmu00130)
  Tyrosine metabolism (mmu00350)
  Phenylalanine metabolism (mmu00360)
  Metabolic pathways (mmu01100)
• Reactome Pathway: Tyrosine catabolism (R-HSA-8963684)
• BioCyc Pathway: MetaCyc:HS08267-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitisinone	DMVS9WQ	Hereditary tyrosinemia type 1	5C50.11	Approved	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-433771	DME20VP	Respiratory syncytial virus infection	1C80	Terminated	[2]

15 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(4-Hydroxy-phenoxy)-acetic acid	DMRCM5O	Discovery agent	N.A.	Investigative	[3]
2-(2-Bromo-benzoyl)-cyclohexane-1,3-dione	DM3VH7F	Discovery agent	N.A.	Investigative	[4]
2-(2-Chloro-benzoyl)-cyclohexane-1,3-dione	DMG6ABE	Discovery agent	N.A.	Investigative	[4]
2-(2-Iodo-benzoyl)-cyclohexane-1,3-dione	DMSVHU9	Discovery agent	N.A.	Investigative	[4]
2-(2-Methoxy-benzoyl)-cyclohexane-1,3-dione	DMESMBO	Discovery agent	N.A.	Investigative	[4]
2-(2-Methyl-benzoyl)-cyclohexane-1,3-dione	DM4GN0E	Discovery agent	N.A.	Investigative	[4]
2-(2-Nitro-benzoyl)-cyclohexane-1,3-dione	DMUJQX1	Discovery agent	N.A.	Investigative	[4]
2-acetyl-3-hydroxycyclohex-2-enone	DMRKYD6	Discovery agent	N.A.	Investigative	[5]
2-Acetyl-cyclohexane-1,3-dione	DMN8TVB	Discovery agent	N.A.	Investigative	[4]
2-Cyclopropanecarbonyl-cyclohexane-1,3-dione	DMRS6LH	Discovery agent	N.A.	Investigative	[4]
2-Propionyl-cyclohexane-1,3-dione	DMP8J7E	Discovery agent	N.A.	Investigative	[4]
3-hydroxy-2-propionylcyclohex-2-enone	DMEK9DH	Discovery agent	N.A.	Investigative	[5]
3-Hydroxy-4-phenyl-5H-furan-2-one	DM5QZDL	Discovery agent	N.A.	Investigative	[3]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[6]
Diketonitrile	DMPKQER	Discovery agent	N.A.	Investigative	[7]

References

• [1] Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. Expert Opin Pharmacother. 2008 May;9(7):1229-36.
• [2] Emerging drugs for respiratory syncytial virus infection. Expert Opin Emerg Drugs. 2009 Jun;14(2):207-17.
• [3] Design, synthesis, and evaluation of postulated transient intermediate and substrate analogues as inhibitors of 4-hydroxyphenylpyruvate dioxygenase. Bioorg Med Chem Lett. 2002 Jul 8;12(13):1709-13.
• [4] SAR studies of 2-o-substituted-benzoyl- and 2-alkanoyl-cyclohexane-1,3-diones as inhibitors of 4-hydroxyphenylpyruvate dioxygenase. Bioorg Med Chem Lett. 2000 May 1;10(9):843-5.
• [5] Enzyme inhibition potency enhancement by active site metal chelating and hydrogen bonding induced conformation-restricted cyclopropanecarbonyl deri... Bioorg Med Chem Lett. 2006 Dec 1;16(23):6024-7.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] 4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target. Drug News Perspect. 2003 Oct;16(8):493-6.