Telotristat ethyl

Chemical compound From Wikipedia, the free encyclopedia

Telotristat ethyl (USAN, brand name Xermelo) is a prodrug of telotristat, which is an inhibitor of tryptophan hydroxylase. It is formulated as telotristat etiprate — a hippurate salt of telotristat ethyl.[3]

Trade namesXermelo
Other namesLX1032, LX1606
AHFS/Drugs.comMonograph
MedlinePlusa617029
Quick facts Clinical data, Trade names ...
Telotristat ethyl
Clinical data
Trade namesXermelo
Other namesLX1032, LX1606
AHFS/Drugs.comMonograph
MedlinePlusa617029
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding>99% (both telotristat ethyl and telotristat)
MetabolismHydrolysis via carboxylesterases
MetabolitesTelotristat
Elimination half-life0.6 hours (telotristat ethyl), 5 hours (telotristat)
ExcretionFeces (92.8%), urine (less than 0.4%)[3]
Identifiers
  • [(S)-Ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate]
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC27H26ClF3N6O3
Molar mass574.99 g·mol−1
3D model (JSmol)
  • CCOC(=O)C(CC1=CC=C(C=C1)C2=CC(=NC(=N2)N)OC(C3=C(C=C(C=C3)Cl)N4C=CC(=N4)C)C(F)(F)F)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
  • Key:MDSQOJYHHZBZKA-GBXCKJPGSA-N
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On February 28, 2017, the U.S. Food and Drug Administration (FDA) approved telotristat ethyl in combination with somatostatin analog (SSA) therapy for the treatment of adults with diarrhea associated with carcinoid syndrome that SSA therapy alone has inadequately controlled.[5][6] Telotristat ethyl was approved for use in the European Union in September 2017.[4]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[7]

Pharmacology

Telotristat is an inhibitor of tryptophan hydroxylase,[8] which mediates the rate-limiting step in serotonin biosynthesis.[3]

Action of telotristat on tryptophan hydroxylase

Adverse effects

Common adverse effects noted in clinical trials include nausea, headache, elevated liver enzymes, depression, accumulation of fluid causing swelling (peripheral edema), flatulence, decreased appetite, and fever. Constipation is also common, and may be serious or life-threatening (especially in overdose).[5]

Formulations

It is marketed by Lexicon Pharmaceuticals (as telotristat etiprate). 328 mg telotristat etiprate is equivalent to 250 mg telotristate ethyl.[3]

Telotristat etiprate

References

Further reading

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