Target Information
| Target General Information | Top | |||||
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| Target ID |
T78915
(Former ID: TTDI01969)
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| Target Name |
Tryptophan 5-hydroxylase 1 (TPH1)
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| Synonyms |
Tryptophan 5-monooxygenase 1; TRPH; TPRH
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| Gene Name |
TPH1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Psychotic disorder [ICD-11: 6A20-6A25] | |||||
| 2 | Pulmonary hypertension [ICD-11: BB01] | |||||
| 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.
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| BioChemical Class |
Paired donor oxygen oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.14.16.4
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| Sequence |
MIEDNKENKDHSLERGRASLIFSLKNEVGGLIKALKIFQEKHVNLLHIESRKSKRRNSEF
EIFVDCDINREQLNDIFHLLKSHTNVLSVNLPDNFTLKEDGMETVPWFPKKISDLDHCAN RVLMYGSELDADHPGFKDNVYRKRRKYFADLAMNYKHGDPIPKVEFTEEEIKTWGTVFQE LNKLYPTHACREYLKNLPLLSKYCGYREDNIPQLEDVSNFLKERTGFSIRPVAGYLSPRD FLSGLAFRVFHCTQYVRHSSDPFYTPEPDTCHELLGHVPLLAEPSFAQFSQEIGLASLGA SEEAVQKLATCYFFTVEFGLCKQDGQLRVFGAGLLSSISELKHALSGHAKVKPFDPKITC KQECLITTFQDVYFVSESFEDAKEKMREFTKTIKRPFGVKYNPYTRSIQILKDTKSITSA MNELQHDLDVVSDALAKVSRKPSI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T39T57 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | AGN-2979 | Drug Info | Phase 2 | Psychotic disorder | [1] | |
| 2 | KAR5585 | Drug Info | Phase 1 | Pulmonary arterial hypertension | [2] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | AGN-2979 | Drug Info | [1] | |||
| Inhibitor | [+] 3 Inhibitor drugs | + | ||||
| 1 | 6-fluorotryptophan | Drug Info | [3] | |||
| 2 | alpha-propyldopacetamide | Drug Info | [4] | |||
| 3 | fenclonine | Drug Info | [4] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 2 BioCyc Pathways | + | ||||
| 1 | Superpathway of tryptophan utilization | |||||
| 2 | Serotonin and melatonin biosynthesis | |||||
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Tryptophan metabolism | |||||
| 2 | Metabolic pathways | |||||
| 3 | Serotonergic synapse | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | 5-Hydroxytryptamine biosynthesis | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Tryptophan Metabolism | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | Biogenic Amine Synthesis | |||||
| 3 | Tryptophan metabolism | |||||
| 4 | Metabolism of amino acids and derivatives | |||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 3 | (+)-6-fluorotryptophan, an inhibitor of tryptophan hydroxylase: sleep and wakefulness in the rat. Neuropharmacology. 1981 Apr;20(4):335-9. | |||||
| REF 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). | |||||
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