Telotristat

Summary

Telotristat (CHEMBL2103855) is an approved small molecule (ATC A16AX15) targeting TPH1; indicated across 5 conditions including carcinoid syndrome and ulcerative colitis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A16AX15
• Targets: 1 (TPH1)
• Indications: 5 conditions
• Clinical trials: 1
• Chemistry: 546.9 Da · C25H22ClF3N6O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2103855
Name	Telotristat
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	25025298
ATC	A16AX15
Molecular formula	C25H22ClF3N6O3
Molecular weight	546.9
InChIKey	NCLGDOBQAWBXRA-PGRDOPGGSA-N

SMILES: CC1=NN(C=C1)C2=C(C=CC(=C2)Cl)[C@H](C(F)(F)F)OC3=NC(=NC(=C3)C4=CC=C(C=C4)C[C@@H](C(=O)O)N)N

IUPAC name: (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]propanoic acid

Also known as: LP 778902, LP-778902, LX-3033, Telotristat, TELOTRISTAT, telotristat

Parent form; salt/anhydrous children: CHEMBL4796268

Patent coverage: 124 distinct patent families (310 SureChEMBL compound mentions), from 1 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: 15 (assay-derived). Sample: Cholecystokinin receptor type A, Prothrombin, D(1A) dopamine receptor, Estrogen receptor, Prostaglandin G/H synthase 1, Sodium-dependent noradrenaline transporter, Type-1 angiotensin II receptor, Sodium-dependent serotonin transporter, Prostaglandin G/H synthase 2, D(3) dopamine receptor.

Bioactivity

ChEMBL activities: 12 potent at pChembl ≥ 5 of 22 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TPH1	7.8	IC50	16	nM	CHEMBL_ACT_16472555
TPH1	7.8	IC50	16	nM	CHEMBL_ACT_16582746
TPH2	6.15	IC50	710	nM	CHEMBL_ACT_24826752
TPH2	6.15	IC50	710	nM	CHEMBL_ACT_25666115
TPH1	6.11	IC50	770	nM	CHEMBL_ACT_24826714
TPH1	6.11	IC50	770	nM	CHEMBL_ACT_25666042
PTGS1	5.79	AC50	1620	nM	CHEMBL_ACT_25205184
Q63921	5.62	AC50	2400	nM	CHEMBL_ACT_25174186
PTGS1	5.62	AC50	2390	nM	CHEMBL_ACT_25206117
ADORA3	5.57	AC50	2700	nM	CHEMBL_ACT_25133996
PTGS2	5.32	AC50	4800	nM	CHEMBL_ACT_25165982
SLC6A2	5.03	AC50	9360	nM	CHEMBL_ACT_25145960

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

5 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 syndrome	3	MONDO:0100347	EFO:1000852
ulcerative colitis	2	MONDO:0005101	EFO:0000729
neuroendocrine neoplasm	2	MONDO:0019496	EFO:1001901
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086

Clinical trials

Total trials: 1.

Phase distribution

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04543955	PHASE2	TERMINATED	Telotristat With Lutathera in Neuroendocrine Tumors

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.

3 molecules share ≥1 primary target. Top 3 by shared-target count:

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