Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUHP71)

• DTT Name: Tyrosine 3-monooxygenase (TH)
• Synonyms: Tyrosine 3-hydroxylase; TH
• Gene Name: TH
• DTT Type: Successful target; [1]
• Related Disease:
  Adrenomedullary hyperfunction [ICD-11: 5A75]
  Nutritional deficiency [ICD-11: 5B50-5B71]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: TY3H_HUMAN
• TTD ID: T62390
• EC Number: EC 1.14.16.2
• Sequence:
  MPTPDATTPQAKGFRRAVSELDAKQAEAIMVRGQGAPGPSLTGSPWPGTAAPAASYTPTP
  RSPRFIGRRQSLIEDARKEREAAVAAAAAAVPSEPGDPLEAVAFEEKEGKAVLNLLFSPR
  ATKPSALSRAVKVFETFEAKIHHLETRPAQRPRAGGPHLEYFVRLEVRRGDLAALLSGVR
  QVSEDVRSPAGPKVPWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQVYRQRRKLIAEI
  AFQYRHGDPIPRVEYTAEEIATWKEVYTTLKGLYATHACGEHLEAFALLERFSGYREDNI
  PQLEDVSRFLKERTGFQLRPVAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPDCC
  HELLGHVPMLADRTFAQFSQDIGLASLGASDEEIEKLSTLYWFTVEFGLCKQNGEVKAYG
  AGLLSSYGELLHCLSEEPEIRAFDPEAAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYAS
  RIQRPFSVKFDPYTLAIDVLDSPQAVRRSLEGVQDELDTLAHALSAIG
• Function: Plays an important role in the physiology of adrenergic neurones.
• KEGG Pathway:
  Tyrosine metabolism (hsa00350)
  Metabolic pathways (hsa01100)
  Dopaminergic synapse (hsa04728)
  Prolactin signaling pathway (hsa04917)
  Parkinson's disease (hsa05012)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Alcoholism (hsa05034)
• Reactome Pathway: Catecholamine biosynthesis (R-HSA-209905)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-Phenylalanine	DMQXI9F	Malnutrition	5B50-5B71	Approved	[2], [3], [4]
L-tyrosine	DM9O8DT	Malnutrition	5B50-5B71	Approved	[3], [4]
Metyrosine	DMBYCU0	Pheochromocytoma	5A75	Approved	[1]
Tetrahydrobiopterin	DMINZ4W	Malnutrition	5B50-5B71	Approved	[5]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L1-79	DMLHPVW	Autism spectrum disorder	6A02	Phase 2	[6]
OXB-102	DMXF9DM	Parkinson disease	8A00.0	Phase 1/2	[7]
ProSavin	DMJ42E6	Parkinson disease	8A00.0	Phase 1/2	[8]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-chlorotyrosine	DMJ4SDM	Discovery agent	N.A.	Investigative	[9]
3-iodotyrosine	DMNZMH6	Discovery agent	N.A.	Investigative	[9]
7,8-dihydrobiopterin	DMQU4XM	Discovery agent	N.A.	Investigative	[10]
alpha-propyldopacetamide	DMQKMX3	Discovery agent	N.A.	Investigative	[9]
Meta-Tyrosine	DM0748C	Discovery agent	N.A.	Investigative	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Parkinson's disease	8A00.0	Substantia nigra tissue	9.10E-04	-2.73	-1.55

References

• [1] Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Hypertension. 1991 Jul;18(1):1-8.
• [2] Selectivity and affinity determinants for ligand binding to the aromatic amino acid hydroxylases. Curr Med Chem. 2007;14(4):455-67.
• [3] Effect of metals and phenylalanine on the activity of human tryptophan hydroxylase-2: comparison with that on tyrosine hydroxylase activity. Neurosci Lett. 2006 Jul 3;401(3):261-5.
• [4] In situ and in vitro evidence for DCoH/HNF-1 alpha transcription of tyrosinase in human skin melanocytes. Biochem Biophys Res Commun. 2003 Feb 7;301(2):610-6.
• [5] Biochemistry of postmortem brains in Parkinson's disease: historical overview and future prospects. J Neural Transm Suppl. 2007;(72):113-20.
• [6] Effect of L1-79 on Core Symptoms of Autism Spectrum Disorder: A Case Series. Clin Ther. 2019 Oct;41(10):1972-1981.
• [7] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [8] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [9] URL: 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. (Target id: 1243).
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.