Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLSWP6)

• DTT Name: GTP cyclohydrolase-I (GCH1)
• Synonyms: Guanosine triphosphate cyclohydrolase I; GTP-CH-I; GTP cyclohydrolase I; GTP cyclohydrolase 1; GCH; DYT5
• Gene Name: GCH1
• DTT Type: Clinical trial target; [1]
• Related Disease: Parkinsonism [ICD-11: 8A00]
• BioChemical Class: Carbon-nitrogen hydrolase
• UniProt ID: GCH1_HUMAN
• TTD ID: T28226
• EC Number: EC 3.5.4.16
• Sequence:
  MEKGPVRAPAEKPRGARCSNGFPERDPPRPGPSRPAEKPPRPEAKSAQPADGWKGERPRS
  EEDNELNLPNLAAAYSSILSSLGENPQRQGLLKTPWRAASAMQFFTKGYQETISDVLNDA
  IFDEDHDEMVIVKDIDMFSMCEHHLVPFVGKVHIGYLPNKQVLGLSKLARIVEIYSRRLQ
  VQERLTKQIAVAITEALRPAGVGVVVEATHMCMVMRGVQKMNSKTVTSTMLGVFREDPKT
  REEFLTLIRS
• Function: May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown. Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs).
• KEGG Pathway:
  Folate biosynthesis (hsa00790)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation (R-HSA-1474151)
• BioCyc Pathway: MetaCyc:HS05586-MON

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Guanine	DMIWLJE	N. A.	N. A.	Phase 3	[1]
OXB-102	DMXF9DM	Parkinson disease	8A00.0	Phase 1/2	[2]
ProSavin	DMJ42E6	Parkinson disease	8A00.0	Phase 1/2	[3]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-Propanol, Isopropanol	DML5O0H	Discovery agent	N.A.	Investigative	[4]
8-hydroxyguanine	DMT9BPN	Discovery agent	N.A.	Investigative	[1]
Guanosine-5'-Triphosphate	DMV2OJX	Discovery agent	N.A.	Investigative	[5]

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	3.38E-02	-1.59	-1.53

References

• [1] GTP cyclohydrolase I feedback regulatory protein-dependent and -independent inhibitors of GTP cyclohydrolase I. Arch Biochem Biophys. 2001 Apr 1;388(1):67-73.
• [2] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [3] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [4] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.