Tryptophan hydroxylase 1
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
A cytosolic aromatic amino-acid hydroxylase requiring tetrahydrobiopterin and iron; converts tryptophan to 5-hydroxytryptophan, which is then decarboxylated to serotonin.
- 3 · How drugs use it
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.
External identifiers
Biology
A cytosolic aromatic amino-acid hydroxylase requiring tetrahydrobiopterin and iron; converts tryptophan to 5-hydroxytryptophan, which is then decarboxylated to serotonin.
- Enterochromaffin cells of the gut and pineal gland
- Serotonin-secreting neuroendocrine tumours
Latest papers
topQuery 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.
Similar pages
not linked directly; found by shared links- TreatmentSomatostatin analogues (octreotide, lanreotide)
Shares Carcinoid syndrome and carcinoid heart disease, Telotristat ethyl, Somatostatin receptor 2, Neuroendocrine tumours.
- IdeaSSTR antagonist radioligands to increase tumour dose
- TargetDopamine D2 receptor
- CompanyPOINT Biopharma
- TrialNETTER-1
- PersonMartyn E. Caplin
- PersonJonathan R. Strosberg
- CompanyRadioMedix