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Tryptophan hydroxylase makes serotonin, the hormone that neuroendocrine tumours pour out in carcinoid syndrome; telotristat ethyl blocks the enzyme to cut the diarrhoea that somatostatin analogues leave uncontrolled.
Tryptophan hydroxylase 1 is the rate-limiting enzyme for serotonin synthesis outside the brain, chiefly in the enterochromaffin cells of the gut. Metastatic neuroendocrine tumours that keep this machinery release large amounts of serotonin, causing the diarrhoea, flushing and eventual heart-valve fibrosis of carcinoid syndrome. Telotristat ethyl, approved in the United States and Europe in 2017, inhibits TPH1 peripherally and reduced bowel movement frequency in the TELESTAR trial when added to somatostatin analogues; it does not cross into the brain, so the brain isoform TPH2 and mood are spared.
In plain words · Tryptophan hydroxylase makes serotonin, the hormone that neuroendocrine tumours pour out in carcinoid syndrome; telotristat ethyl blocks the enzyme to cut the diarrhoea that somatostatin analogues leave uncontrolled.
Tryptophan hydroxylase makes serotonin, the hormone that neuroendocrine tumours pour out in carcinoid syndrome; telotristat ethyl blocks the enzyme to cut the diarrhoea that somatostatin analogues leave uncontrolled.
A cytosolic aromatic amino-acid hydroxylase requiring tetrahydrobiopterin and iron; converts tryptophan to 5-hydroxytryptophan, which is then decarboxylated to serotonin.
No product in this corpus aims at Tryptophan hydroxylase 1 yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Tumour-associated overexpression: HPA finds the RNA cancer enhanced in cancer (Uterine Corpus Endometrial Carcinoma (TCGA)) and group enriched in normal choroid plexus, intestine, stomach 1, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA TPH1: RNA group enriched (choroid plexus 6 nTPM, intestine 19 nTPM, stomach 1 15 nTPM); no normal tissue stained high; highest cancer staining colorectal cancer (8 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Neuroendocrine tumours); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas TPH1 tissue; Human Protein Atlas TPH1 pathology; Open Targets ENSG00000129167 associations
First described 1990. Earliest sequence paper UniProt cites for the protein: Boulalard et al, Nucleic Acids Res, 1990, "Complete coding sequence of human tryptophan hydroxylase". Source.
A cytosolic aromatic amino-acid hydroxylase requiring tetrahydrobiopterin and iron; converts tryptophan to 5-hydroxytryptophan, which is then decarboxylated to serotonin.
RNA: group enriched (choroid plexus 6 nTPM, intestine 19 nTPM, stomach 1 15 nTPM), detected in some normal tissues.
No normal tissue stained high.
RNA cancer enhanced: Uterine Corpus Endometrial Carcinoma 5 pTPM.
Medium only: glioma, head and neck cancer, lung cancer, lymphoma.
HPA TPH1 tissue · HPA TPH1 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Neuroendocrine tumours | host% | Host target: serotonin synthesis in enterochromaffin cells. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"Tryptophan hydroxylase 1" OR ABSTRACT:"Tryptophan hydroxylase 1" OR TITLE:"TPH1" OR ABSTRACT:"TPH1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Tryptophan hydroxylase 1, not a curated reading list.
Shares Telotristat ethyl, Neuroendocrine tumours.