TELOTRISTAT ETHYL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H26ClF3N6O3
Molecular Weight	574.982
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=MDSQOJYHHZBZKA-GBXCKJPGSA-N

InChI=1S/C27H26ClF3N6O3/c1-3-39-25(38)20(32)12-16-4-6-17(7-5-16)21-14-23(35-26(33)34-21)40-24(27(29,30)31)19-9-8-18(28)13-22(19)37-11-10-15(2)36-37/h4-11,13-14,20,24H,3,12,32H2,1-2H3,(H2,33,34,35)/t20-,24+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C27H26ClF3N6O3
Molecular Weight	574.982
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.openaccessjournals.com/articles/telotristat-etiprate-a-novel-inhibitor-of-serotonin-synthesis-for-the-treatment-of-carcinoid-syndrome.pdf
Curator's Comment: Description was created using several sources including: http://www.lexpharma.com/media-center/news/525-fda-extends-pdufa-date-for-telotristat-etiprate-for-the-treatment-of-carcinoid-syndrome; https://www.ncbi.nlm.nih.gov/pubmed/25012985

Telotristat (telotristat etiprate) is an ethyl ester prodrug which is hydrolyzed to its active moiety LP-778902 both in vivo and in vitro. Telotristat etiprate is an orally bioavailable, small-molecule, tryptophan hydroxylase (TPH) inhibitor. It is the first investigational drug in clinical studies to target TPH, an enzyme that triggers the excess serotonin production within metastatic neuroendocrine tumor (mNET) cells leading to carcinoid syndrome. Unlike existing treatments of carcinoid syndrome which reduce the release of serotonin outside tumor cells, telotristat etiprate reduces serotonin production within the tumor cells. By specifically inhibiting serotonin production telotristat may provide patients with more control over their disease. Telotristat etiprate has received Fast Track and Orphan Drug designation from the U.S. Food and Drug Administration and has been granted priority review by the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of February 28, 2017.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Carboxylesterase 2 9 Target ID: CHEMBL2217 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf	Substrate 661
tryptophan hydroxylase 2 4 Target ID: 121278.0 Gene Symbol: TPH2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf	Inhibitor 8504	1210.0 nM [IC50]
tryptophan hydroxylase 1 4 Target ID: 7166.0 Gene Symbol: TPH1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf	Inhibitor 8504	800.0 nM [IC50]
tryptophan hydroxylase 2 4 Target ID: 121278.0 Gene Symbol: TPH2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf	Inhibitor 8504	32.0 nM [IC50]
tryptophan hydroxylase 1 4 Target ID: 7166.0 Gene Symbol: TPH1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf	Inhibitor 8504	28.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Carcinoid syndrome 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf	Curative		Approved 8583	XERMELO Approved Use Xermelo is a tryptophan hydroxylase inhibitor indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy. Launch Date 2017

C_max

Value	Dose	Co-administered	Analyte	Population
610 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TELOTRISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
2320 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TELOTRISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TELOTRISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TELOTRISTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
500 mg 3 times / day steady, oral Highest studied dose Dose: 500 mg, 3 times / day Route: oral Route: steady Dose: 500 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25636046	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://pubmed.ncbi.nlm.nih.gov/25636046	Disc. AE: Abdominal pain, Shortness of breath... AEs leading to discontinuation/dose reduction: Abdominal pain (1 patient) Shortness of breath (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/25636046
500 mg 3 times / day steady, oral Highest studied dose Dose: 500 mg, 3 times / day Route: oral Route: steady Dose: 500 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000MedR.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000MedR.pdf	Disc. AE: Gastrointestinal disorders, Skin and subcutaneous tissue disorders... AEs leading to discontinuation/dose reduction: Gastrointestinal disorders (7.1%) Skin and subcutaneous tissue disorders (1.4%) Cardiac disorders (1.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000MedR.pdf
250 mg 3 times / day steady, oral Recommended Dose: 250 mg, 3 times / day Route: oral Route: steady Dose: 250 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000MedR.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000MedR.pdf	Disc. AE: Abdominal pain, GGT increased... AEs leading to discontinuation/dose reduction: Abdominal pain (4.3%) GGT increased (2.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000MedR.pdf
250 mg 3 times / day steady, oral Recommended Dose: 250 mg, 3 times / day Route: oral Route: steady Dose: 250 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000MedR.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000MedR.pdf	Disc. AE: Gastrointestinal disorders, Psychiatric disorders... AEs leading to discontinuation/dose reduction: Gastrointestinal disorders (10%) Psychiatric disorders (2.9%) Infections and infestations (2.9%) Skin and subcutaneous tissue disorders (1.4%) Hepatobiliary disorders (1.4%) Metabolism and nutrition disorders (1.4%) Renal and urinary disorders (1.4%) Respiratory, thoracic and mediastinal disorders (1.4%) Vascular disorders (1.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000MedR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057 CYP2C8 1057 CYP2E1 1060 CYP2B6 926 P-gp 1741 BCRP 910 OCT1 620 OCT2 779 OAT1 725 OAT3 747 OATP1B1 1079 OATP1B3 961 BSEP 550	P-gp 2052 BCRP 697	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=8 Page: 7.0	likely
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=8 Page: 7.0	likely	TELOTRISTAT 4
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=8 Page: 7.0	likely
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=8 Page: 7.0	likely	TELOTRISTAT 4
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=8 Page: 7, 38	likely
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=8 Page: 7.0	likely	TELOTRISTAT 4
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	no	TELOTRISTAT 4
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	no	TELOTRISTAT 4
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	no	TELOTRISTAT 4
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	no	TELOTRISTAT 4
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	no	TELOTRISTAT 4
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely	TELOTRISTAT 4
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely	TELOTRISTAT 4
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely	TELOTRISTAT 4
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely	TELOTRISTAT 4
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely	TELOTRISTAT 4
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely	TELOTRISTAT 4
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	unlikely	TELOTRISTAT 4
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	weak
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	weak	TELOTRISTAT 4
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	weak
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	weak
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	weak	TELOTRISTAT 4
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	weak	TELOTRISTAT 4
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf#page=10 Page: 10.0	yes
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	yes
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36.0	yes	TELOTRISTAT 4
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=29 Page: 36, (ClinPharm) 28-30, 38	yes		no (co-administration study) Comment: 79% inihibition at 1 mcM, 30 min incubation (cytochrome P450isozymes using specific fluorometric substrates or human liver microsomal samples w/LC-MS/MS analysis), When 3 mg midazolam was coadministered orally after 5 day treatment with telotristat ethyl 500 mg three times daily (twice the recommended dosage), the mean Cmax , and AUC0-inf for midazolam were decreased by 25%, and 48%, respectively, compared to administration of midazolam alone. The mean Cmax , and AUC0-inf for the active metabolite, 1’-hydroxymidazolam, were also decreased by 34%, and 48%, respectively. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=29 Page: 36, (ClinPharm) 28-30, 38
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=31 Page: 30-31, 39	yes		unlikely (co-administration study) Comment: Following co-administration with telotristat ethyl (500 mg TID x 5 days (twice the recommended dose)), mean Cmax, and AUC0-inf for fexofenadine (180 mg with the final dose of telotristat ethyl) were 15.6%, and 14.3% higher, respectively compared to administration alone. Telotristat ethyl exhibited a lower level of P-gp inhibition in humans (<1.25-fold) that not clinically meaningful. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000ClinPharmR.pdf#page=31 Page: 30-31, 39

Drug as victim

Target	Modality	Activity	Metabolite
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36-37	likely	TELOTRISTAT 4
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36-37	no
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36-37	no	TELOTRISTAT 4
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=43 Page: 36-37	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=32 Page: 25.0
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208794Orig1s000PharmR.pdf#page=32 Page: 25.0		TELOTRISTAT 4

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA008TH4	https://www.aablocks.com/goods/Goods/detail?id=AA008TH4
abcr GmbH	AB463154	http://www.abcr.com/shop/en/AB463154
ApexBio Technology	B3247	http://www.apexbt.com/telotristat.html
BioCrick	BCC5128	http://www.biocrick.com/Telotristat-BCC5128.html
Chem Scene	CS-2408	http://www.chemscene.com/1033805-28-5.html
Chemspace	CSSB00025704745	https://chem-space.com/CSSB00025704745
DC Chemicals	DC23164	http://www.dcchemicals.com/product_show-DC23164.html
eNovation Chemicals	D552488	https://www.enovationchem.com/ProductDetails.asp?ProductID=D552488
eNovation Chemicals	D678474	https://www.enovationchem.com/ProductDetails.asp?ProductID=D678474
Excenen	EX-A1620	http://www.excenen.com/searchresultlist.php?id=1033805-28-5
Lab Network	LN01306658	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01306658
MedChem Express	HY-13055B	https://www.medchemexpress.com/telotristat.html
Smolecule	S544877	http://www.smolecule.com/products/s544877
Smolecule	S746675	https://www.smolecule.com/products/s746675
THE BioTek	bt-283998	https://www.thebiotek.com/product/inhibitors/bt-283998

PubMed

Title	Date	PubMed
Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide.	2014-10	25012985

Patents

Sample Use Guides

In Vivo Use Guide

Two 250 mg telotristat etiprate tablets three times daily over 12 weeks

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:56:52 GMT 2025` Edited by `admin` on `Mon Mar 31 19:56:52 GMT 2025`
Record UNII	8G388563M7
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LX 1032

Preferred Name

English

TELOTRISTAT ETHYL

Official Name

English

LX 1606

Code

English

LX-1032

Code

English

TELOTRISTAT ETHYL [USAN]

Common Name

English

Telotristat ethyl [WHO-DD]

Common Name

English

L-PHENYLALANINE, 4-(2-AMINO-6-((1R)-1-(4-CHLORO-2-(3-METHYL-1H-PYRAZOL-1-YL)PHENYL)-2,2,2-TRIFLUOROETHOXY)-4-PRYRIMIDINYL)-, ETHYL ESTER

Common Name

English

LX1606

Code

English

ETHYL 4-(2-AMINO-6-((1R)-1-(4-CHLORO-2-(3-METHYL-1H-PYRAZOL-1-YL)PHENYL)-2,2,2-TRIFLUOROETHOXY)PRYRIMIDIN-4-YL)-L-PHENYLALANINATE

Common Name

English

TELOTRISTAT ETHYL [MI]

Common Name

English

LX-1606

Code

English

LX1032

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C471