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

DTT Name Tryptophan 5-hydroxylase 1 (TPH1)
Synonyms Tryptophan 5-monooxygenase 1; TRPH; TPRH
Gene Name TPH1
DTT Type
Clinical trial target
[1]
BioChemical Class
Paired donor oxygen oxidoreductase
UniProt ID
TPH1_HUMAN
TTD ID
T78915
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 1.14.16.4
Sequence
MIEDNKENKDHSLERGRASLIFSLKNEVGGLIKALKIFQEKHVNLLHIESRKSKRRNSEF
EIFVDCDINREQLNDIFHLLKSHTNVLSVNLPDNFTLKEDGMETVPWFPKKISDLDHCAN
RVLMYGSELDADHPGFKDNVYRKRRKYFADLAMNYKHGDPIPKVEFTEEEIKTWGTVFQE
LNKLYPTHACREYLKNLPLLSKYCGYREDNIPQLEDVSNFLKERTGFSIRPVAGYLSPRD
FLSGLAFRVFHCTQYVRHSSDPFYTPEPDTCHELLGHVPLLAEPSFAQFSQEIGLASLGA
SEEAVQKLATCYFFTVEFGLCKQDGQLRVFGAGLLSSISELKHALSGHAKVKPFDPKITC
KQECLITTFQDVYFVSESFEDAKEKMREFTKTIKRPFGVKYNPYTRSIQILKDTKSITSA
MNELQHDLDVVSDALAKVSRKPSI
Function
Responsible for addition of the -HO group (hydroxylation) to the 5 position to form the amino acid 5-hydroxytryptophan (5-HTP), which is the initial and rate-limiting step in the synthesis of the neurotransmitter serotonin.
KEGG Pathway
Tryptophan metabolism (hsa00380 )
Metabolic pathways (hsa01100 )
Serotonergic synapse (hsa04726 )
Reactome Pathway
NGF-stimulated transcription (R-HSA-9031628 )
Serotonin and melatonin biosynthesis (R-HSA-209931 )
BioCyc Pathway
MetaCyc:HS05250-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AGN-2979 DMLQRFO Psychotic disorder 6A20-6A25 Phase 2 [1]
KAR5585 DMXYN1H Pulmonary arterial hypertension BB01.0 Phase 1 [2]
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3 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
6-fluorotryptophan DM6YD3U Discovery agent N.A. Investigative [3]
alpha-propyldopacetamide DMQKMX3 Discovery agent N.A. Investigative [4]
fenclonine DMUBO3E Discovery agent N.A. Investigative [4]
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The Drug-Metabolizing Enzyme (DME) Role of This DTT

DTT DME Name Tryptophan 5-hydroxylase 1 (TPH1) DME Info
Gene Name TPH1
1 Approved Drug(s) Metabolized by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
L-Tryptophan DMIBH7M Depression 6A70-6A7Z Approved [5]
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References

1 Antidepressant-like action of AGN 2979, a tryptophan hydroxylase activation inhibitor, in a chronic mild stress model of depression in rats. Eur Neuropsychopharmacol. 2001 Oct;11(5):351-7.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 (+)-6-fluorotryptophan, an inhibitor of tryptophan hydroxylase: sleep and wakefulness in the rat. Neuropharmacology. 1981 Apr;20(4):335-9.
4 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: 1241).
5 Developmental role of tryptophan hydroxylase in the nervous system. Mol Neurobiol. 2007 Feb;35(1):45-54.