U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C27H26ClF3N6O3.C9H9NO3
Molecular Weight 754.155
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TELOTRISTAT ETIPRATE

SMILES

OC(=O)CNC(=O)C1=CC=CC=C1.CCOC(=O)[C@@H](N)CC2=CC=C(C=C2)C3=CC(O[C@H](C4=C(C=C(Cl)C=C4)N5C=CC(C)=N5)C(F)(F)F)=NC(N)=N3

InChI

InChIKey=XSFPZBUIBYMVEA-CELUQASASA-N
InChI=1S/C27H26ClF3N6O3.C9H9NO3/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;11-8(12)6-10-9(13)7-4-2-1-3-5-7/h4-11,13-14,20,24H,3,12,32H2,1-2H3,(H2,33,34,35);1-5H,6H2,(H,10,13)(H,11,12)/t20-,24+;/m0./s1

HIDE SMILES / InChI

Molecular Formula C9H9NO3
Molecular Weight 179.1727
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
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

Curator's Comment: The molecule was designed not to cross the blood-brain barrier at the intended dose, and preclinical studies suggested that telotristat etiprate acts primarily peripherally, with little, if any, activity observed in the central nervous system.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
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

1.48815361E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
610 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
2320 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
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

Doses

DosePopulationAdverse 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:
unhealthy, adult
n = 14
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 14
Sources:
Disc. AE: Abdominal pain, Shortness of breath...
AEs leading to
discontinuation/dose reduction:
Abdominal pain (1 patient)
Shortness of breath (1 patient)
Sources:
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
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:
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:
unhealthy, adult
n = 140
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 140
Sources:
Disc. AE: Abdominal pain, GGT increased...
AEs leading to
discontinuation/dose reduction:
Abdominal pain (4.3%)
GGT increased (2.1%)
Sources:
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
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:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 1 patient
Disc. AE
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:
unhealthy, adult
n = 14
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 14
Sources:
Shortness of breath 1 patient
Disc. AE
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:
unhealthy, adult
n = 14
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 14
Sources:
Cardiac disorders 1.4%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Skin and subcutaneous tissue disorders 1.4%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Gastrointestinal disorders 7.1%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
GGT increased 2.1%
Disc. AE
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:
unhealthy, adult
n = 140
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 140
Sources:
Abdominal pain 4.3%
Disc. AE
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:
unhealthy, adult
n = 140
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 140
Sources:
Hepatobiliary disorders 1.4%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Metabolism and nutrition disorders 1.4%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Renal and urinary disorders 1.4%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Respiratory, thoracic and mediastinal disorders 1.4%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Skin and subcutaneous tissue disorders 1.4%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Vascular disorders 1.4%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Gastrointestinal disorders 10%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Infections and infestations 2.9%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Psychiatric disorders 2.9%
Disc. AE
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:
unhealthy, adult
n = 70
Health Status: unhealthy
Condition: carcinoid syndrome
Age Group: adult
Population Size: 70
Sources:
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
likely
likely
likely
likely
likely
likely
no
no
no
no
no
no
no
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
weak
weak
weak
weak
weak
weak
yes
yes
yes
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.
Page: 36, (ClinPharm) 28-30, 38
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.
Page: 30-31, 39
Drug as victimTox targets
PubMed

PubMed

TitleDatePubMed
Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide.
2014 Oct
Patents

Sample Use Guides

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 Sat Dec 17 03:42:29 UTC 2022
Edited
by admin
on Sat Dec 17 03:42:29 UTC 2022
Record UNII
3T25U84H4U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TELOTRISTAT ETIPRATE
USAN   WHO-DD  
USAN  
Official Name English
LX 1032 HIPPURATE
Code English
LX1032 HIPPURATE
Code English
Telotristat etiprate [WHO-DD]
Common Name English
LX-1606 HIPPURATE
Code English
LX-1032 HIPPURATE
Code English
TELOTRISTAT ETIPRATE [USAN]
Common Name 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 N-BENZOYLGLYCINATE (1:1)
Common Name English
TELOTRISTAT ETIPRATE [ORANGE BOOK]
Common Name English
TELOTRISTAT ETIPRATE [MI]
Common Name English
XERMELO
Brand Name English
LX1606 HIPPURATE
Code English
TELOTRISTAT ETHYL HIPPURATE
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, COMPD. WITH N-BENZOYLGLYCINE (1:1)
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C471
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
EU-Orphan Drug EU/3/09/661
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
FDA ORPHAN DRUG 266308
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
Code System Code Type Description
MERCK INDEX
M12015
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
RXCUI
1872448
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
EVMPD
SUB182048
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
EPA CompTox
DTXSID701027870
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
FDA UNII
3T25U84H4U
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
NCI_THESAURUS
C81941
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
CAS
1137608-69-5
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
DAILYMED
3T25U84H4U
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
PUBCHEM
25253377
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
DRUG BANK
DBSALT002591
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
USAN
WW-147
Created by admin on Sat Dec 17 03:42:29 UTC 2022 , Edited by admin on Sat Dec 17 03:42:29 UTC 2022
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY