{"entity":{"id":"tph1","kind":"target","name":"Tryptophan hydroxylase 1","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tryptophan_hydroxylase_1","links":[{"label":"UniProt P17752: TPH1","url":"https://www.uniprot.org/uniprotkb/P17752/entry"},{"label":"HGNC:12008 TPH1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12008"},{"label":"ChEMBL target CHEMBL3831287","url":"https://www.ebi.ac.uk/chembl/explore/target/CHEMBL3831287"}],"tags":["chembl-gap"],"related":["sstr2"],"cancers":["neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":["telotristat-ethyl"],"companies":[],"institutions":[],"pathways":[],"terms":["carcinoid-syndrome"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"notes":[],"symbol":"TPH1","biology":"A cytosolic aromatic amino-acid hydroxylase requiring tetrahydrobiopterin and iron; converts tryptophan to 5-hydroxytryptophan, which is then decarboxylated to serotonin.","whereFound":["Enterochromaffin cells of the gut and pineal gland","Serotonin-secreting neuroendocrine tumours"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/tph1/","neighbours":{"target":[{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","route":"/targets/sstr2/"}],"cancer":[{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"}],"drug":[{"id":"telotristat-ethyl","kind":"drug","name":"Telotristat ethyl","route":"/drugs/telotristat-ethyl/"}],"term":[{"id":"carcinoid-syndrome","kind":"term","name":"Carcinoid syndrome and carcinoid heart disease","route":"/terms/carcinoid-syndrome/"}]}}