Details of the Drug Therapeutic Target (DTT)

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]
Related Disease	Psychotic disorder [ICD-11: 6A20-6A25] Pulmonary hypertension [ICD-11: BB01]
BioChemical Class	Paired donor oxygen oxidoreductase
UniProt ID	TPH1_HUMAN
TTD ID	T78915
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
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.