Telotristat Ethyl

Summary

Telotristat Ethyl (CHEMBL2105695) is an approved small molecule targeting TPH1; indicated across 6 conditions including carcinoid heart disease and carcinoid syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 1 (TPH1)
• Indications: 6 conditions
• Clinical trials: 10
• Chemistry: 575 Da · C27H26ClF3N6O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2105695
Name	Telotristat Ethyl
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	25181577
Molecular formula	C27H26ClF3N6O3
Molecular weight	575
InChIKey	MDSQOJYHHZBZKA-GBXCKJPGSA-N

SMILES: CCOC(=O)[C@H](CC1=CC=C(C=C1)C2=CC(=NC(=N2)N)O[C@H](C3=C(C=C(C=C3)Cl)N4C=CC(=N4)C)C(F)(F)F)N

IUPAC name: ethyl (2S)-2-amino-3-[4-[2-amino-6-[(1R)-1-[4-chloro-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl]phenyl]propanoate

Also known as: LX 1032, LX 1606, LX-1032, LX-1606, LX1032, LX1606, Telotristat ethyl, Xermelo, TELOTRISTAT ETHYL, TELOTRISTAT-ETHYL, LX1606 hippurate, telotristat ethyl

Parent form; salt/anhydrous children: CHEMBL3348963

Patent coverage: 76 distinct patent families (191 SureChEMBL compound mentions), from 2 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
TPH1	L-Tryptophan hydroxylase 1	Inhibition	7.19	0.3%	P17752

Broader ChEMBL bioactivity targets: 17 (assay-derived). Sample: 5-hydroxytryptamine receptor 3A, Cholecystokinin receptor type A, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Glucocorticoid receptor, Motilin receptor, Sodium-dependent noradrenaline transporter, Type-1 angiotensin II receptor, Sodium-dependent serotonin transporter, Sodium-dependent dopamine transporter.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 17 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TPH2	6.14	IC50	730	nM	CHEMBL_ACT_27984047
TPH1	6.11	IC50	770	nM	CHEMBL_ACT_27983921
ADORA3	5.51	AC50	3100	nM	CHEMBL_ACT_25134657
PDE4D	5.3	AC50	5000	nM	CHEMBL_ACT_25185785
CCKAR	5	AC50	10000	nM	CHEMBL_ACT_25178636

Target pathways

Aggregated over 1 target gene(s): TPH1.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Serotonin and melatonin biosynthesis	1	TPH1
NGF-stimulated transcription	1	TPH1

Dominant GO biological processes

GO term	Targets
platelet degranulation	1
obsolete serotonin biosynthetic process from L-tryptophan	1
serotonin biosynthetic process	1
positive regulation of fat cell differentiation	1
bone remodeling	1
mammary gland alveolus development	1
regulation of hemostasis	1
aromatic amino acid metabolic process	1
phenol-containing compound biosynthetic process	1

Indications & clinical

Indications

6 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
carcinoid heart disease	3	MONDO:0043529	EFO:1001769
carcinoid syndrome	2	MONDO:0100347	EFO:1000852
neuroendocrine neoplasm	2	MONDO:0019496	EFO:1001901
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
liver disorder	1	MONDO:0005154	EFO:0001421

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 10.

Phase distribution

Phase	Trials
PHASE2	4
PHASE3	2
PHASE1	2
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04810091	PHASE3	ACTIVE_NOT_RECRUITING	Telotristat Ethyl for the Treatment of Carcinoid Heart Disease in Patients With Metastatic Neuroendocrine Tumor
NCT04065165	PHASE3	WITHDRAWN	Lanreotide Combined With Telotristat Ethyl or Placebo for the First-line Treatment in Patients With Advanced Well Differentiated Small Intestinal Neuroendocrine Tumours (siNET) With Highly-functioning Carcinoid Syndrome
NCT03790111	PHASE2	TERMINATED	A Safety and Efficacy Study of XERMELO® + First-line Chemotherapy in Patients With Advanced Biliary Tract Cancer
NCT03910387	PHASE2	COMPLETED	Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer
NCT04713202	PHASE2	WITHDRAWN	Prospective Assessment of Patients With Neuroendocrine Tumors and Current or Prior History of Carcinoid Syndrome or Diarrhea Undergoing Peptide Receptor Radionuclide Therapy With or Without Telotristat Ethyl
NCT04776876	PHASE2	WITHDRAWN	Retifanlimab (INCMGA00012) and Telotristat Ethyl for the Treatment of Advanced Neuroendocrine Tumors and Carcinoid Syndrome
NCT03302845	PHASE1	COMPLETED	A Phase 1 Study to Evaluate the Effects of Omeprazole and Famotidine on the Absorption of Telotristat Ethyl in Healthy Subjects
NCT03423446	PHASE1	COMPLETED	Study to Evaluate the Pharmacokinetics of Telotristat Ethyl in Subjects With Severe Hepatic Impairment
NCT03223428	Not specified	COMPLETED	Real-world Evidence Study EvaLuating PAtient-Reported Outcomes With XERMELO
NCT04034745	Not specified	WITHDRAWN	Open Label Study to Analyze the Effect of Telotristat Ethyl on Weight Regulation/Gain

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

2 molecules share ≥1 primary target. Top 2 by shared-target count:

Molecule	Source	Status	Shared targets
TELOTRISTAT	ChEMBL + PubChem	Phase 4 (approved)	TPH1
RODATRISTAT	ChEMBL	Phase 2	TPH1